Thermoregulatory vs. event sweating--comparison of clinical methodologies, physiology and results.

OBJECTIVES: Although the mechanisms of sweating due to thermoregulation vs. stress are distinct, the antiperspirant industry focuses primarily on perspiration due to heat as their method of efficacy testing. To better understand the overall protection afforded by a 'Clinical Strength' over-the-counter antiperspirant product, we compare results from a standard hot-room study with results from two studies using the Trier Social Stress Test (TSST). METHODS: For each study, unscented antiperspirant was applied to one axilla, leaving the other untreated for internal control. The hot-room protocol involved a 40-min warm-up period with 2-20 min sweat collections at 100 ± 2 °F (35% RH). The TSST requires naïve subjects to give an impromptu speech and conduct mental arithmetic, with collections of sweat, heart rate and other biomarkers of stress before, during and after the event. RESULTS: During the TSST, heart rate and salivary cortisol data indicate significant emotional stress. Wetness results show that sweat was reduced by 69.4% in the hot-room study, compared with 83.7% and 89.3% reductions in the stress studies. CONCLUSION: We have found added value in investigating antiperspirancy from several causes of sweat production to give a more encompassing picture of the protection afforded by an antiperspirant product, specifically wetness protection from heat, activity and stress-induced sweat.

Age-dependent effects on cisapride-induced QTc prolongation in the isolated guinea pig heart.

INTRODUCTION: The isolated guinea pig heart preparation has been suggested as a suitable small animal model for investigating potential for QTc prolongation. The purpose of this study was to investigate the effect of age on electrophysiological parameters measured in the isolated guinea pig heart preparation. In addition, the effect of a compound known to prolong the QT interval (cisapride) was investigated in both young and adult guinea pigs. METHODS: Male guinea pigs were divided into 2 groups (n=6). One group of guinea pigs was between 3 and 4 weeks old (young) and the other group was between 16 and 17 weeks old (adult). Concentrations (0, 1, 5, and 50 ng/mL; 2, 11, and 110 nM) of cisapride were perfused for 15 min from low to high concentration. Measurements of PR, QRS, RR and QT intervals were typically made on 5 consecutive electrocardiogram complexes during the last minute of each concentration. The QT interval was corrected for changes in heart rate using the cube root formula of Fridericia (QTcF). RESULTS: Adult guinea pigs had significantly longer RR and QTcF intervals when compared to young animals. Cisapride prolonged QTcF in both young and adult animals at the same concentrations (5 ng/mL and 50 ng/mL). The maximal change in QTcF at 50 ng/mL was similar in young (44+/-3 ms) and adult animals (40+/-1 ms). DISCUSSION: In summary, the present study demonstrated that there was an increase in the RR and QTcF intervals with age in isolated guinea pig hearts. However, this age difference does not appear to impact the sensitivity of the assay to drug-induced QTcF prolongation.

Effects of fasting on evaluation of gastrointestinal transit with charcoal meal.

INTRODUCTION: At the present time, most studies investigating gastrointestinal transit time with charcoal are conducted in fasted rats. It seems reasonable to hypothesize that the fasting state of rats could influence the effect a compound had on gastrointestinal transit time. The purpose of this study was to investigate the effects of food on the pharmacological effects on gastrointestinal transit. METHODS: For each drug investigated, two sets of 32 male Sprague-Dawley rats were used. One set was studied after being fasted for approximately 6 h, the second set was studied after free access to food. Each set had 4 groups of animals (n=8/group) that were administered different doses, allowing the assessment of the drug effect after fasting and after free access to food. Animals were administered 0, 10, 25, and 75 mg/kg of morphine; 0, 10, 20, and 40 mg/kg loperamide, or 0, 0.05, 0.5, and 3.0 mg/kg clonidine. At predetermined times, an activated charcoal suspension was administered by oral gavage. Thirty minutes after receiving the charcoal meal, rats were euthanized and the small intestine was removed. The length of the small intestine and the distance traveled by the charcoal were recorded. For each animal, gastrointestinal transit was calculated as the percentage of the distance traveled relative to the total length of the small intestine. RESULTS: Baseline (vehicle dosed animals) gastrointestinal transit was significantly greater in fasted versus fed rats. In fasted rats, morphine did not have a significant effect on transit. In fed rats, 25 and 75 mg/kg morphine caused a significant decrease in transit. In fed and fasted rats, 0.5 and 3 mg/kg clonidine caused a significant decrease in transit. Loperamide did not affect gastrointestinal transit in fed or fasted rats at doses up to 40 mg/kg. DISCUSSION: These data demonstrate that food does not reduce the sensitivity of the gastrointestinal transit time.

Novel methods to evaluate controlled reperfusion techniques in cardiac surgery.

BACKGROUND: This manuscript describes two novel techniques that may be useful for comparing methods to reperfuse the heart during cardiac operations. These techniques are based on measurements of intra-myocyte ion content and the analysis of reperfusion arrhythmias. METHODS: Myocyte ion content was measured in normal porcine hearts before and after ischemia (cardioplegic arrest, CP arrest) using atomic absorption spectroscopy. A cobalt-EDTA complex served as the extra-cellular marker. Cobalt-EDTA was infused into the aorta together with blood or cardioplegia (CP) solution. Myocardial biopsies were taken prior to CP arrest and upon successful defibrillation 5 min after initiating reperfusion. Ventricular fibrillation (VF) was recorded prior to ischemia, and then during reperfusion. VF wavefront (WF) morphology and propagation patterns were analyzed using computer algorithms. Electrophysiologic variables for measuring VF included the multiplicity index (a descriptor of VF organization), the number of WFs detected (nwaves/s) and the mean peak first derivative of electrogram voltage with respect to time (mp d V/dt). RESULTS: Intra-cellular sodium content increased, while intra-cellular magnesium content decreased between control and reperfusion measurements (p < 0.05). Electrophysiologic recovery was characterized by increasingly rapid depolarization (i.e. more negative mp d V/dt) and an increasing nwaves/s during the first minute of post-CP reperfusion. CONCLUSIONS: Atomic absorption spectroscopy and computer-based analysis of reperfusion VF successfully measured metabolic and electrophysiologic events that occurred during controlled reperfusion. These methods may be useful for comparing controlled reperfusion techniques.

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.

Ventricular assist devices as a bridge to cardiac transplantation. A prelude to destination therapy.

OBJECTIVE AND BACKGROUND: Ventricular assist devices (VADs) have been used for temporary circulatory support pending transplantation or recovery of the native heart. Outcome in 38 patients treated at the authors' institution with VADs pending transplantation was analyzed to provide information relevant to the future use of VADs as permanent implants. METHODS: Thoratec (Thoratec Laboratories, Pleasanton, CA) or HeartMate (Thermo Cardiosystems, Woburn, MA) VADs were used in all cases. Patients were considered for VAD placement if they were candidates for cardiac transplantation and fulfilled the criteria for the Food and Drug Administration investigational Device Exemption trials. The following adverse events were included in the analysis; death during VAD support, device malfunction, bleeding, neurologic events, support-related events that preclude transplantation, and device-related infections. Patient survival and complication rates were quantified using the Kaplan-Meier method, competing risk analysis, and hazard functions. RESULTS: Nineteen patients had transplantation. Three patients had VAD removal after cardiac recovery and 16 died without transplantation. The duration of VAD support ranged from 0 to 279 days. The hazard function for death during VAD support had an early phase that lasted for 2 weeks after VAD placement, and early death was related to the preimplant condition of the patient. Device-related infections were noted in 11 patients. Seven of these patients had transplantation after clearing the infection, whereas four died without transplantation. Neurologic events occurred in seven patients. There were no device malfunctions that led to patient death. CONCLUSIONS: The absence of fatal device malfunctions suggests that longer term support with current VAD designs is feasible. Appropriate patient selection, infection control, and avoidance of thromboembolic neurologic complications will be crucial to the success of permanent VAD use.

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.

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.

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.

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.

Electrophysiological mechanisms for postcardioplegia reperfusion ventricular fibrillation.

BACKGROUND: Reperfusion arrhythmias that follow regional ischemia at normothermia have been studied extensively and are considered to be a manifestation of ischemia-reperfusion injury. In contrast, reperfusion arrhythmias that occur following hypothermic cardioplegic arrest have received little attention from investigators. This study defines the electrophysiological mechanisms for postcardioplegia reperfusion ventricular fibrillation (RVF). METHODS AND RESULTS: The electrophysiology of postcardioplegia RVF was examined by using in situ porcine hearts. Complete heart block was created by using cryoablation before cardioplegic arrest so that isolated ventricular electrical activity could be observed for a prolonged time after reperfusion. Electrophysiological data were collected from limb leads, right atrial electrodes, and left ventricular electrodes in all 12 pigs. In 5 pigs, right and left ventricular endocardial electrograms were also recorded. A total of 103 episodes of RVF were analyzed. In 90 instances, an accelerating automatic ventricular focus initiated RVF. In five animals, RVF occurred after ventricular pacing (ie, purely re-entrant RVF). The mechanism for RVF was indeterminant in 8 instances. The origin of RVF was mapped in 44 instances. RVF usually originated in the left ventricle (25 instances) or septum (16 instances). CONCLUSIONS: Enhanced automaticity and re-entry are the mechanisms for postcardioplegia and regional ischemia-reperfusion arrhythmias. This finding supports the use of postcardioplegia RVF as a variable for comparing strategies for myocardial protection and suggests that information generated by the study of regional ischemia reperfusion arrhythmias can be used to understand postcardioplegia reperfusion arrhythmias and ischemia-reperfusion injury.

Effect of hemoglobin concentration on oxyhemoglobin dissociation during hypothermic blood cardioplegic arrest.

BACKGROUND: This study compares oxyhemoglobin dissociation during the nonperfused periods of hypothermic cardioplegic arrest in two blood cardioplegic solutions with different hemoglobin concentrations. The hypothesis is that more oxygen will dissociate from hemoglobin in a blood cardioplegic solution with a higher hemoglobin content than from a cardioplegic solution with a lower hemoglobin content. However, the increment in the volume of oxygen that dissociates from hemoglobin will be less than anticipated by a ratio of hemoglobin concentrations in the cardioplegic solution. METHODS AND RESULTS: Pigs (n = 22) were supported by bypass and subjected to 60 minutes of hypothermic cardioplegic arrest with either a high-hemoglobin (n = 10) or low-hemoglobin (n = 12) blood cardioplegic solution. Aortic root and coronary sinus blood samples were obtained before bypass and 5 seconds after the start of cardioplegic infusions at 20, 40, and 60 minutes of cardioplegic arrest. Oxyhemoglobin dissociation occurred in both experimental groups during the ischemic intervals of cardioplegic arrest. However, there were no significant differences between the high- and low-hemoglobin groups in the arterial-venous oxygen content differences for samples taken after each of the three ischemic intervals (p values: control = 0.78; cardioplegia interval 1 = 0.95; interval 2 = 0.56; and interval 3 = 0.12). CONCLUSIONS: The present study emphasizes the inherent limitations of unmodified erythrocyte hemoglobin as an oxygen source in hypothermic alkalotic cardioplegic solutions. These limitations may be obviated by methods that increase the dissolved oxygen content of the cardioplegic solution or methods that decrease the affinity of hemoglobin for oxygen under conditions of hypothermia and alkalosis.

Effect of postcardioplegia reperfusion rhythm on myocardial blood flow.

This study compared myocardial blood flow during postcardioplegia reperfusion asystole and ventricular fibrillation. Pigs (n = 20) were placed on cardiopulmonary bypass and blood cardioplegic solution at 38 degrees C was then infused. A preischemia microsphere injection was given in asystolic hearts. All animals then had 1 hour of hypothermic cardioplegic arrest and underwent reperfusion with high-dose (n = 10) or low-dose (n = 10) 38 degrees C blood cardioplegia. At 30 seconds after reperfusion, all hearts were asystolic. The second microsphere injection was then given. At 3 and 6 minutes after reperfusion, the animals' hearts were either in asystole (n = 10) or ventricular fibrillation (n = 10), and the third and fourth microsphere injections were then given. At 10 minutes after reperfusion, all hearts were beating and the final (fifth) microsphere injection was given. There was an initial increase in the global myocardial blood flow during reperfusion versus the preischemic control value. However, later, during reperfusion (ie, at the third and fourth injections), there was a significant (p < 0.05) decrease in the global myocardial blood flow. There was no discernible response in either the global myocardial blood flow or regional myocardial blood flow distribution to electromechanical activity (ie, ventricular fibrillation) for the third and fourth injections, suggesting that coronary autoregulation was abnormal. Postcardioplegia reperfusion ventricular fibrillation imposes metabolic demands that may cause reperfusion injury, especially in hearts affected by hypertrophy, ventricular distention, or coronary obstruction.

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.

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.

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.

Duration of asystolic reperfusion and reperfusate electrolyte composition influence postcardioplegia ventricular fibrillation.

The conditions of postcardioplegia reperfusion that influence cardiac electrophysiologic recovery have not yet been fully elucidated. Studies of postcardioplegia electrophysiologic recovery and reperfusion-induced arrhythmias, particularly reperfusion-induced ventricular fibrillation, are useful for improving our understanding of reperfusion injury since reperfusion-induced arrhythmias are sensitive indicators for reperfusion injury. The purpose of this study was to determine the effects of asystolic reperfusion and reperfusate electrolyte composition on postcardioplegia electrophysiologic recovery of the heart. The hypothesis tested is that the duration of asystolic reperfusion produced by a hyperkalemic reperfusate is a primary determinant for the return of cardiac electrical activity without reperfusion-induced ventricular fibrillation and that reperfusion with a hypocalcemic-hyperkalemic solution further reduces the prevalence of reperfusion-induced ventricular fibrillation by limiting myocyte calcium exposure during initial postischemic recovery. Fifty-six pigs were supported by cardiopulmonary bypass and subjected to identical conditions of hypothermic cardioplegic arrest. Reperfusion was initiated with unmodified pump blood, a hypocalcemic-normokalemic cardioplegic solution, a hyperkalemic-normocalcemic cardioplegic solution, or a hyperkalemic-hypocalcemic cardioplegic solution. The hyperkalemic-normocalcemic solution was administered at a dose of 500 ml/m2 or 1500 ml/m2. The hyperkalemic-hypocalcemic and hypocalcemic-normokalemic solutions were given only at a dose of 500 ml/m2. All cardioplegic reperfusion solutions were followed by infusion of unmodified pump blood for the remainder of the 15-minute period of controlled reperfusion. Reperfusion-induced ventricular fibrillation was less prevalent in the high-dose hyperkalemic solution group (4/12) than in the low-dose hyperkalemic solution (9/10) or unmodified pump blood (12/12) groups (p < 0.05). The transmyocardial lactate gradient at the time of initial postreperfusion electrical activity was positive (0.21 +/- 0.04 mmol/L) in the high-dose hyperkalemic group and negative (-0.05 +/- 0.09 mmol/L) in the low-dose hyperkalemic group (p < 0.05). Fibrillation was less prevalent in the hypocalcemic-hyperkalemic group (8/12) than in the other groups reperfused with cardioplegic solution at a dose of 500 ml/m2 (hypocalcemic-normokalemic, 10/10; hyperkalemic-normocalcemic, 9/10) or in the group reperfused with unmodified pump blood (12/12) (p < 0.05, hypocalcemic-hyperkalemic group versus other reperfusate groups). Reperfusion-induced ventricular fibrillation is an indicator of reperfusion injury, and in this study the conditions of reperfusion influenced the prevalence of reperfusion-induced ventricular fibrillation. Recovery of aerobic metabolism during hyperkalemia-induced asystolic reperfusion was associated with a lower prevalence of reperfusion-induced ventricular fibrillation. Combining hypocalcemia with hyperkalemia decreased the prevalence of reperfusion-induced ventricular fibrillation.

Oxyhemoglobin dissociation during hypothermic blood cardioplegia arrest.

BACKGROUND: Coronary sinus effluent contains desaturated blood during the first few seconds of hypothermic cardioplegia infusion in humans. This occurs despite the high affinity of hemoglobin for oxygen at a low temperature and alkaline pH. The present study quantitates oxyhemoglobin dissociation during hypothermic cardioplegic arrest. METHODS AND RESULTS: Three infusions of a 4 degrees C alkalotic blood cardioplegia solution were given into the cross-clamped aortic root during 1 hour of cardioplegic arrest. Paired aortic root and coronary sinus blood samples were obtained before and shortly after initiating cardiopulmonary bypass and at t = 5 seconds and 30 seconds during each cardioplegia infusion. Throughout the study, the hemoglobin saturation in the aortic root samples was 100%. The mean coronary sinus hemoglobin saturation at t = 5 seconds during hypothermic cardioplegia infusion ranged from 63.0% to 66.5% (p < 0.05 coronary sinus compared with aortic root samples). The coronary sinus hemoglobin saturation approximated the aortic root hemoglobin saturation at t = 30 seconds during hypothermic cardioplegia infusion. The mean PO2 of the aortic root samples ranged from 214 to 307 mm Hg during hypothermic cardioplegia infusion. The mean PO2 of the t = 5 seconds coronary sinus samples ranged from 31 to 39 mm Hg, whereas the mean PO2 of the t = 30 seconds coronary sinus samples ranged from 85 to 119 mm Hg during cardioplegia infusion (p < 0.05 coronary sinus compared with aortic root samples). CONCLUSIONS: Oxygen dissociates from hemoglobin contained in a hypothermic, alkalotic blood cardioplegia solution during the nonperfused phase of cardioplegic arrest. However, the only oxygen delivered to the myocardium during the infusion of a hypothermic alkalotic blood cardioplegia solution is oxygen physically dissolved in the solution.