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Ikuo Hagino

Publications and source records attributed to Ikuo Hagino.

16 recordsLinked to original sources

Intermediate results of the double-switch operations for atrioventricular discordance.

BACKGROUND: Since 1987, anatomic biventricular repair using the double-switch operations has been our principal choice for patients with atrioventricular discordance. These alternative procedures have the theoretical advantage of using the anatomic left ventricle to support the systemic circulation. METHODS: A total of 45 patients underwent the double-switch operation. Their ages ranged from 6 months to 21 years. Associated malformations included pulmonary atresia in 27, pulmonary stenosis in 11, and Ebstein's malformation in 5. An atrial switch plus an arterial switch procedure was performed in 7, and an atrial switch plus a Rastelli-type ventriculoarterial switch procedure in 38. Follow-up ranged from 6 months to 15 years. RESULTS: Early mortality was 8.9% (n = 4). In the latter half of the series (n = 23, since 1994), there was no early death. Six patients died late. Actuarial survival at 5 and 10 years was 83.6% and 77.6%, respectively. Six patients required conduit replacement, and 2 required revision of an intraatrial baffle for pulmonary venous channel obstruction and infection, respectively. Freedom from reoperation was 95.3% at 5 years and 76.2% at 10 years. Freedom from arrhythmia was 88.8% at 5 years and 78.4% at 10 years. The systemic ventricular ejection fraction was 0.568 +/- 0.103 at 1 year (n = 39), 0.555 +/- 0.105 at 5 years (n = 17), and 0.539 +/- 0.098 at 10 years (n = 12). CONCLUSIONS: The surgical results of the double-switch operations have been improving. Intermediate follow-up suggests that these alternative procedures are a reasonable option for patients with atrioventricular discordance.

Adolescent↗

Biventricular repair for right atrial isomerism.

BACKGROUND: Biventricular repair is often difficult to accomplish in patients with right atrial isomerism because of complex anomalous structures. METHODS: Ten patients with right atrial isomerism underwent biventricular repair. Their ages ranged from 15 months to 21 years. The follow-up period ranged from 1 month to 21 years. The Fontan procedure was unsuitable in 7 patients. The atrioventricular valves were separated in 5 patients and common in 5. One patient who had severe right-sided atrioventricular valvular regurgitation required concomitant prosthetic valve replacement. Another patient with a hypoplastic intraventricular septum underwent ventricular septation. Nine patients had two balanced ventricles. A ventricular septal defect was enlarged for rerouting in 3 patients. All patients had anomalous venoatrial connections and required intra-atrial baffle rerouting. One with major aortopulmonary collateral arteries underwent staged unifocalization. Three had extracardiac conduit repair. The outcomes were compared with 97 patients who underwent the Fontan procedure. RESULTS: There were 3 early deaths and 1 late death. Six survivors are in New York Heart Association functional class I or II. Two are free from medications. Two required reoperation owing to infection or prosthetic valve failure. At 1 year, cardiac index and systemic venous pressure were 3.2 +/- 0.9 L.min(-1).m(-2) and 6.6 +/- 1.6 mm Hg, respectively. There were no significant differences in survival, freedom from arrhythmia, freedom from reoperation, or exercise tolerance between biventricular repair and the Fontan procedure. CONCLUSIONS: Biventricular repair provided good long-term outcomes in patients with right atrial isomerism. In selected circumstances, biventricular repair is an acceptable alternative to the Fontan procedure.

Abnormalities, Multiple↗

Cerebral endothelial nitric oxide synthase expression is reduced after very-low-flow bypass.

BACKGROUND: In previous studies we have shown that delayed capillary reperfusion after low flow bypass predicts neurologic injury. In this acute study, we hypothesized that low flow reduces endothelial nitric oxide synthase (eNOS) expression, which may lead to more profound inflammatory response and delayed capillary perfusion. METHODS: Twelve piglets (13.2 +/- 0.7 kg) had a cranial window placed over the parietal cerebral cortex for direct examination of the microcirculation using intravital fluorescence microscopy. Animals were cooled to 15 degrees C or 34 degrees C on cardiopulmonary bypass (pH stat, hematocrit 30%, pump flow 100 mL/kg/minute) followed by 2 hours of low flow (50 mL/kg/minute) or very low flow (10 mL/kg/minute). Rhodamine staining was used to observe adherent and rolling leukocytes in postcapillary venules. The eNOS protein expression was determined by Western immunoblotting. RESULTS: High temperature and low flow rate correlated with significantly reduced eNOS expression (p < 0.01). Univariate comparisons based on Student t tests indicated that eNOS protein levels were lower at 34 degrees C than at 15 degrees C (0.7 +/- 0.6 vs 1.7 +/- 0.5, p < 0.01) and at 10 mL/kg per minute compared with 50 mL/kg per minute (0.8 +/- 0.7 vs 1.6 +/- 0.5, p = 0.03). Moreover, two-way analysis of variance revealed that temperature (F = 21.6, p < 0.001) and flow rate (F = 13.8, p = 0.005) were independent multivariate predictors of eNOS expression. During low flow bypass, eNOS was inversely correlated with numbers of adherent (p = 0.002) and rolling (p = 0.006) leukocytes, following an exponential decay curve closely. CONCLUSIONS: eNOS expression is reduced after very low flow bypass, particularly at a higher bypass temperature. This is associated with delayed capillary reperfusion. Reduced eNOS is also associated with increased white cell activation which may lead to greater neurologic injury.

Animals↗

Partial anomalous pulmonary venous connection to the superior vena cava.

BACKGROUND: Repair of partial anomalous pulmonary venous connection (PAPVC) to the high portion of the superior vena cava (SVC) may be complicated by atrial arrhythmia and obstruction of the pulmonary veins or SVC. We reviewed our experience with the modified Warden technique, in which the SVC was transected and anastomosed to the right atrial appendage with anterior augmentation of pedicled autologous pericardial flap, and the atrial septum was directly displaced to the SVC orifice. METHODS: Twenty of 51 patients with PAPVC underwent this technique. Mean age was 11.9 years. Follow-up averaged 6.5 years. To quantify the height of insertion of anomalous pulmonary veins, the distance between the highest anomalous pulmonary venous orifice and SVC-right atrial junction was indexed by thoracic vertebral body height (height index). RESULTS: All patients are alive in sinus rhythm. No patients exhibited pulmonary venous obstruction, and mean flow was 0.61 mL. Mean flow of SVC return was 0.79 mL. The SVC occlusion occurred in 2 patients who had persistent left SVC with a good communicating vein. Three patients whose height index exceeded 2.5 successfully underwent catheter intervention at the SVC channel. CONCLUSIONS: Midterm results with the modified Warden technique were satisfactory. Patients with particularly high insertion of anomalous pulmonary veins should be treated and followed with specific caution for preserving an unobstructed caval pathway.

Adolescent↗

Aprotinin improves cerebral protection: evidence from a survival porcine model.

OBJECTIVE: Aprotinin is a serine protease inhibitor used during cardiac surgery to reduce blood loss and preserve platelet function. It has also been shown to reduce leukocyte activation during and after cardiopulmonary bypass. The goal of the study was to test the hypothesis that aprotinin could reduce cerebral injury after low-flow cardiopulmonary bypass and deep hypothermic circulatory arrest. METHODS: Sixteen piglets (mean weight, 13.6 +/- 1.3 kg) were randomly assigned to receive aprotinin or placebo (8 animals per group) before a 120-minute period of deep hypothermic circulatory arrest (15 degrees C) or 25 mL x kg(-1) x min(-1) low-flow cardiopulmonary bypass (25 degrees C or 34 degrees C). Piglets had a cranial window placed over the parietal cerebral cortex for direct examination of the microcirculation by means of intravital microscopy. Rhodamine-stained leukocytes were observed in postcapillary venules, with analysis for adhesion and rolling. Plasma was labeled with fluorescein isothiocyanate-dextran for assessment of functional capillary density. Neurologic and histologic scores were used as the primary outcome measures. RESULTS: During rewarming, the mean number of both rolling and adherent leukocytes was significantly lower after aprotinin administration (P < .05). At 5 and 15 minutes of rewarming, functional capillary density recovered faster with aprotinin treatment (P < .05). Functional outcome (neurologic deficit score) on postoperative day 1 was significantly improved in aprotinin-treated piglets (P < .05). CONCLUSIONS: Aprotinin reduces inflammation and improves neurologic outcome after a prolonged period of deep hypothermic circulatory arrest or low-flow cardiopulmonary bypass.

Animals↗

Improved outcome with composite graft versus homograft root replacement for children with aortic root aneurysms.

OBJECTIVE: Review of surgical repair of aortic root aneurysms using composite graft or homograft in children. METHODS: A consecutive series of 34 children (mean age 10.8+/-5.4 years) who underwent elective aortic root replacement using composite graft or homograft from 1987 to 2003 (mean follow-up 5.7+/-3.7 years). RESULTS: Preoperatively, the aortic annulus and aortic root average z-scores were 4.1+/-2.2 and 9.4+/-4.7, respectively. Composite graft root replacement was performed in 22 patients, and cryopreserved aortic homograft root replacement in 12 patients. There was one perioperative death in the homograft group due to sudden cardiovascular collapse. There was one late death in the composite graft group due to acute aortic dissection, and two late deaths in the homograft root replacement group, one at 7 months postoperatively due to coronary artery thrombosis and one due to severe chronic myocardial dysfunction 5 years postoperatively. One patient who initially had a homograft died due to mechanical valve thrombosis following reoperative composite graft replacement. Five patients had reoperations at a median of 7.1 years after initial surgery. One patient in the composite graft group underwent arch replacement. There were no graft related reoperations after composite graft root replacement, but 4 patients in the homograft group had reoperative composite graft replacement. Predictors of reoperation included age at surgery, lower weight, and longer ICU time (P<0.05). CONCLUSIONS: In children with aortic root aneurysms, reoperation is more common after homograft root replacement than composite graft replacement. Composite graft root replacement provides more stable repair of the aortic root.

Adolescent↗

Specific bypass conditions determine safe minimum flow rate.

BACKGROUND: The purpose of this study is to define a safe minimum flow rate for specific bypass conditions using continuous monitoring with near-infrared spectroscopy and direct observation of the cerebral microcirculation. METHODS: Two series of experiments (n = 72 in each) were conducted in which piglets were cooled to a temperature of 15 degrees, 25 degrees, or 34 degrees C on cardiopulmonary bypass with hematocrit 20% or 30%, pH-stat management in all, followed by 1 or 2 hours of reduced flow (10, 25, or 50 mL.kg(-1).min(-1)). Animals in series one had a cranial window placed over the parietal cortex to evaluate the microcirculation with intravital microscopy. Plasma was labeled with fluorescein-isothiocyanate-dextran for assessment of functional capillary density (FCD) and microvascular diameter. In series two, near-infrared spectroscopy was utilized to detect tissue oxygenation index (TOI). Outcome measures included histologic and neurologic injury scores. RESULTS: The TOI during low flow and FCD during rewarming and after weaning from cardiopulmonary bypass were associated with neurologic injury. Failure of FCD to return to baseline during rewarming predicted worse functional and histologic outcome (p < 0.001). Regression analysis indicated that temperature and low-flow rate were multivariable predictors of TOI and FCD during rewarming (p < 0.001). CONCLUSIONS: Tissue oxygen index derived from near-infrared spectroscopy is a useful real-time monitor for detecting inadequate cerebral perfusion during cardiopulmonary bypass. Minimal safe pump flow rate varies according to the conditions of bypass: using pH stat management and with an hematocrit of either 20% or 30%, a flow rate as low as 10 mL.kg(-1).min(-1) is safe for as long as 2 hours at a temperature of 15 degrees C. However, under the same conditions at 34 degrees C, a flow rate of 10 mL.kg(-1).min(-1) is very likely to be associated with neurologic injury.

Animals↗

Long-term outcome of right ventricular outflow tract reconstruction using a handmade tri-leaflet conduit.

OBJECTIVE: Since 1985, we have implanted handmade tri-leaflet conduits made of heterologous pericardium or expanded polytetrafluoroethylene (ePTFE), as an alternative to homograft for right ventricular outflow tract reconstruction. This report assesses the long-term outcome of these prostheses. METHODS: From 1985 to 2003, 216 handmade tri-leaflet conduits were implanted in 191 patients. Forty-two patients had previous conduit repairs. The mean age at operation was 8.1+/-7.7 years (range: 15 days-44 years). The underlying diagnoses were pulmonary atresia with ventricular septal defect in 83 patients, atrioventricular discordance in 36, transposition of the great arteries in 26, double outlet right ventricle in 14, and truncus arteriosus in 17. Whole heterologous pericardial tri-leaflet conduits were implanted in 169 patients, in the early series (porcine: 85; equine: 58; bovine: 26); bovine pericardial conduits containing ePTFE leaflets were implanted in 26 patients since 1996; whole ePTFE tri-leaflet rolls were employed in the most recent 21 patients. The conduit size was 21.1+/-3.1mm (range: 12-27 mm), 147.4+/-21.4% (range: 82.6-202.6%) of the anticipated diameter of the pulmonary valve. Follow-up was complete. RESULTS: There were 28 early deaths and 24 late deaths. The indication for conduit replacement was a peak instantaneous pressure gradient of greater than 50 mmHg. Sixty-five conduits required reoperation for conduit obstruction at 8.6+/-3.3 years after implantation. The freedom from reoperation at 5, 10, and 15 years was 93.9+/-1.9, 61.4+/-4.5, and 35.5+/-5.6%, respectively. Patients with smaller conduit size and young age at operation were predisposed to reoperation. None of the 47 ePTFE tri-leaflet conduits developed significant obstruction. The freedom from important pulmonary valve regurgitation (PR) as assessed by echocardiography was 68.3+/-3.7% at 5 years, 33.0+/-4.5% at 10 years, and 21.6+/-4.9% at 15 years. No patient required reoperation due to PR or right ventricular dysfunction. CONCLUSIONS: Handmade tri-leaflet conduits provide a reliable alternative for RVOT reconstruction in children, yielding as good a long-term outcome as do homografts. Longer follow-up is needed to determine how well ePTFE leaflets will fare.

Adolescent↗

Tissue oxygenation index is a useful monitor of histologic and neurologic outcome after cardiopulmonary bypass in piglets.

OBJECTIVE: Tissue oxygenation index is a novel monitoring indicator derived by near-infrared spectroscopy. We hypothesized that tissue oxygenation index could predict a minimum safe flow rate for specific bypass conditions. METHODS: Thirty-six piglets (age, 43 +/- 5 days; weight, 9.0 +/- 1.1 kg) underwent cardiopulmonary bypass with cerebral near-infrared spectroscopy (NIRO-300; Hamamatsu Photonics K.K., Hamamatsu City, Japan). Animals were cooled for 40 minutes to 15 degrees C, 25 degrees C, or 34 degrees C (pH-stat, hematocrit value of 20% or 30%, and pump flow of 100 mL . kg -1 . min -1), followed by low-flow perfusion (10, 25, or 50 mL . kg -1 . min -1) for 2 hours. Neurologic and behavioral evaluations were determined for 4 days. The brain was then fixed for histologic assessment. Tissue oxygenation index was defined as the average signal during low-flow bypass. RESULTS: Animals with an average tissue oxygenation index of less than 55% showed cerebral injury, whereas animals with an index of greater than 55% showed minimal or no evidence of injury. Correlations were found between average tissue oxygenation index and histologic score (Spearman rho = -0.65, P < .001) and neurologic deficit score (Pearson r = -0.50, P = .002) on the first postoperative day. Temperature (P < .001), flow rate (P < .001), and hematocrit value (P = .002) were multivariable predictors of tissue oxygenation index, as determined by means of multivariable analysis of variance. CONCLUSION: Tissue oxygenation index is a useful monitor for defining the minimum safe flow rate during cardiopulmonary bypass. An index value of less than 55% is a strong predictor of neurologic injury.

Animals↗

Fontan operation with a viable and growing conduit using pedicled autologous pericardial roll: serial changes in conduit geometry.

OBJECTIVE: We sought to examine midterm results of the Fontan operation with an extracardiac conduit using pedicled autologous pericardial roll, with special attention to angiographic evaluation of serial changes in conduit geometry. METHODS: Of 202 patients subjected to the Fontan operation since 1996, the conduit was used in 28 patients who had intact pericardium. We retrospectively reviewed a consecutive series of these patients, and serial changes in conduit geometry were accessed in 16 patients who underwent catheter examinations twice at 1.1 +/- 0.4 and 4.5 +/- 1.4 years postoperatively. RESULTS: There was one early and one late death. Except for a patient with apicocaval juxtaposition in whom a conduit occlusion developed caused by compression between the vertebral bodies and the ventricle, there were no important complications. Angiographically, conduit volume, estimated by using the MULTI-SLICE method, increased significantly (3490 +/- 2166 to 5426 +/- 3081 mm3, P < .001), whereas the volume per body weight remained unchanged. Conduit diameter increased significantly at both the inferior vena caval end (16.8 +/- 4.8 to 19.8 +/- 4.8 mm, P < .001) and the pulmonary artery end (11.9 +/- 3.8 to 14.2 +/- 4.2 mm, P < .001), whereas the diameter indexed to the normal right pulmonary artery remained unchanged. The cross-sectional area of the conduit increased in parallel with that of the normal right pulmonary artery. The ratio of the widest to the narrowest diameter of the conduit exhibited no significant change. CONCLUSIONS: Midterm results of the Fontan operation with pedicled autologous pericardial roll were favorable. Proportional increase of conduit size was demonstrated, with its shape preserved. This suggested a potential of the conduit to grow and that growth correlated with somatic development.

Adolescent↗

Higher bypass temperature correlates with increased white cell activation in the cerebral microcirculation.

OBJECTIVE: Cardiopulmonary bypass induces a systemic inflammatory response, which in turn promotes a cascade of leukocyte and endothelial cell activity. We investigated whether differences in bypass temperature and flow rate affect endothelial cell and leukocyte adhesion in the cerebral microcirculation. METHODS: Thirty-six piglets (13.0 +/- 1.1 kg) had a cranial window placed over the parietal cortex to evaluate the microcirculation by means of intravital microscopy. Animals were cooled to a temperature of 15 degrees C, 25 degrees C, or 34 degrees C on cardiopulmonary bypass with hematocrit levels of 20% or 30% by using pH-stat management, followed by 60 minutes of reduced flow (10, 25, or 50 mL.kg(-1).min(-1)). Rhodamine staining was used to observe adherent and rolling leukocytes in postcapillary venules. RESULTS: Higher bypass temperature correlated with significantly more adherent and rolling leukocytes during the full 60 minutes of low-flow bypass (P <.05). Poisson regression revealed more adherent leukocytes at 34 degrees C than at 15 degrees C and at a flow rate of 10 mL.kg(-1).min(-1) compared with a flow rate of 50 mL.kg(-1).min(-1). There was an inverse correlation between flow rate and the number of adherent and rolling leukocytes at 30, 45, and 60 minutes of low-flow bypass (P <.05). Temperature was a multivariable predictor of histologic score, with greater neurologic damage found after bypass at 34 degrees C (P <.01). CONCLUSIONS: Leukocyte activation in cerebral microcirculation is increased with higher temperature and lower flow rate, suggesting that these variables influence the inflammatory response during cardiopulmonary bypass.

Animals↗

Effects of hemodilution and phenylephrine on cerebral blood flow and metabolism during cardiopulmonary bypass.

OBJECTIVE: Hypotension resulting from hemodilution on cardiopulmonary bypass is often treated by pressor (eg, phenylephrine) infusion. The effect of phenylephrine on cerebral blood flow (CBF) in this setting is not clear. It was hypothesized that phenylephrine might decrease CBF. MEASUREMENTS AND MAIN RESULTS: Six different radioactively labeled microspheres (15 microm) were used to measure CBF at 6 time points (T) in 9 pigs (mean body weight 11.3 +/- 1.2 kg): T1 baseline before bypass (mean arterial pressure [MAP] 76 +/- 5 mmHg), T2 on mildly hypothermic CPB (34 degrees C, pump flow 100 mL/kg/min, hematocrit 30%, MAP 79 +/- 7 mmHg), T3 after moderate hemodilution with crystalloid (hematocrit 20%, resulting MAP 62 +/- 6 mmHg), T4 after phenylephrine administration to increase MAP to baseline values (hematocrit 20%), T5 after severe hemodilution (hematocrit 10%, resulting MAP 41 +/- 4 mmHg), and T6 after phenylephrine administration to normalize MAP (hematocrit 10%). In addition, blood flow to liver, small bowel and skeletal muscle, and pH of jugular venous blood were measured at each time point. After institution of CPB, the CBF (mL/min/100 g tissue) increased significantly to 53 +/- 9 (baseline levels 44 +/- 8, T1 v T2, p = 0.03). Hemodilution resulted in significant increases in CBF on CPB to 65 +/- 9 and 90 +/- 9 at hematocrit 20% and hematocrit 10%, respectively (T2 v T3, p = 0.03; T3 v T5, p = 0.01) and a progressive fall in jugular venous pH. At each level of hemodilution, phenylephrine resulted in an additional increase in CBF (T4, 74 +/- 8; T6, 108 +/- 12; T3 v T4, p = 0.04; T5 v T6, p = 0.01) but did not improve jugular venous pH. Changes in liver blood flow after hemodilution and vasopressor injection showed a similar pattern to CBF. However, the blood flow to small bowel and skeletal muscle increased with hemodilution but decreased significantly with phenylephrine administration. CONCLUSIONS: Phenylephrine redirects blood flow from the bowel and muscle to the brain and liver. Hemodilution increases CBF and pressor administration further increases CBF by elevating perfusion pressure. Maintenance of a higher hematocrit on CPB increases MAP and should decrease the need for vasopressor administration.

Animals↗

Direct visualization of minimal cerebral capillary flow during retrograde cerebral perfusion: an intravital fluorescence microscopy study in pigs.

BACKGROUND: Retrograde cerebral perfusion (RCP) is used in some centers during aortic arch surgery for brain protection during hypothermic circulatory arrest. It is still unclear however whether RCP provides adequate microcirculatory blood flow at a capillary level. We used intravital microscopy to directly visualize the cerebral capillary blood flow in a piglet model of RCP. METHODS: Twelve pigs (weight 9.7 +/- 0.9 kg) were divided into two groups (n = 6 each): deep hypothermic circulatory arrest (DHCA) and RCP. After the creation of a window over the parietal cerebral cortex, pigs underwent 10 minutes of normothermic bypass and 40 minutes of cooling to 15 degrees C on cardiopulmonary bypass ([CPB] pH-stat, hemocrit 30%, pump flow 100 mL x kg(-1) x min(-1)). This was followed by 45 minutes of DHCA and rewarming on CPB to 37 degrees C. In the RCP group the brain was retrogradely perfused (pump flow 30 mL x kg(-1) x min(-1)) during DHCA through the superior vena cava after inferior vena cava occlusion. Plasma was labeled with fluorescein-isothiocyanate-dextran for assessing microvascular diameter and functional capillary density (FCD), defined as total length of erythrocyte-perfused capillaries per observation area. Cerebral tissue oxygenation was determined by nicotinamide adenine dinucleotide hydrogen (NADH) autofluorescence, which increases during tissue ischemia. RESULTS: During normothermic and hypothermic antegrade cerebral perfusion the FCD did not significantly change from base line (97% +/- 14% and 96% +/- 12%, respectively). During retrograde cerebral perfusion the FCD decreased highly significantly to 2% +/- 2% of base line values (p < 0.001). Thus there was no evidence of significant capillary blood flow during retrograde cerebral perfusion. The microvascular diameter of cerebral arterioles that were slowly perfused significantly decreased to 27% +/- 6% of base line levels during RCP. NADH fluorescence progressively and significantly increased during RCP, indicating poorer tissue oxygenation. At the end of retrograde cerebral perfusion there was macroscopic evidence of significant brain edema. CONCLUSIONS: RCP does not provide adequate cerebral capillary blood flow and does not prevent cerebral ischemia. Prolonged RCP induces brain edema. However, there might be a role for a short period of RCP to remove air and debris from the cerebral circulation after DHCA because retrograde flow could be detected in cerebral arterioles.

Animals↗

Effects of pH management during deep hypothermic bypass on cerebral microcirculation: alpha-stat versus pH-stat.

OBJECTIVE: There is controversy regarding the optimal pH strategy during deep hypothermic bypass in children. We directly visualized the effects of the pH-stat and alpha-stat strategy on cerebral microcirculation (including leukocyte/endothelial cell interactions) in a piglet model using intravital fluorescence microscopy. METHODS: Two groups of 5 piglets (mean weight 9.6+/-1.3 kg) with a cranial window over parietal cerebral cortex underwent 10-minute normothermic bypass, 40-minute cooling on cardiopulmonary bypass ([CPB] Hct 30%, 100 mL/kg/min), 60-minute circulatory arrest at 15 degrees C, and 40-minute rewarming with alpha-stat (group alpha) or pH-stat (group pH). Plasma was labeled with fluorescein-ITC-dextran for assessment of microvascular diameter. Circulating leukocytes were labeled and observed in postcapillary venules for adhesion before and up to 120 minutes after CPB. Cerebral tissue oxygenation was evaluated by quantification of NADH autofluorescence, which increases during ischemia. RESULTS: At the end of normothermic bypass diameter of cerebrocortical microvessels increased to 116+/-9% (alpha) versus 119+/-10% (pH) of pre-CPB baseline values. During cooling microvascular diameter decreased in group alpha and significantly increased in group pH (89+/-11% (alpha) versus 132+/-13% (pH) at the end of cooling; P<0.001). During the first 10 minutes of rewarming, the cerebral microvascular diameter was significantly larger when the pH stat strategy was used. Tissue oxygenation at the end of cooling was significantly greater in the pH-stat group (P=0.008). On reperfusion, the pH-stat strategy resulted in significantly more rapid return of tissue oxygenation toward baseline although at the end of rewarming the metabolic recovery was complete in both groups. The whole body lactate during early rewarming was significantly less with the pH stat strategy. There was no significant difference between the groups regarding the number of adherent leukocytes throughout the time course of the experiment. CONCLUSIONS: pH-stat management increases tissue oxygenation during deep hypothermic bypass and after circulatory arrest. Leukocyte/endothelial cell interactions during hypothermic bypass are mild with both alpha-stat and pH-stat.

Animals↗

The effects of vasoactive intestinal peptide on monocrotaline induced pulmonary hypertensive rabbits following cardiopulmonary bypass: a comparative study with isoproteronol and nitroglycerine.

BACKGROUND: Vasoactive intestinal peptide (VIP) has regulatory effects on myocardial and vasomotor functions usually demonstrated by in vitro or isolated heart studies. We studied in vivo effects in monocrotaline induced pulmonary hypertensive rabbits immediately after cardiopulmonary bypass (CPB) and tested them versus calcium channel and beta-blockers. METHODS: The study consisted of six groups (N=30; five rabbits/group): (1) Control with no pretreatment, monocrotaline injected groups: (solutions were perfused following termination of CPB for 60 min); (2) Control for pulmonary hypertension (PHT); (3) isoproteronol; (4) VIP 10(-6) M; (5) VIP 10(-5) M; (6) nitroglycerine. Normothermic CPB was instituted in thirty rabbits at a flowrate of 100 ml/kg/min for 120 min. Heart rate, mean arterial pressure (MAP), central venous, left atrium (LAP), pulmonary artery (PAP) pressures, pulmonary resistance (Rp), blood gases and ions were measured before and 15, 30, 45 and 60 min after CPB. The VIP 10(-5) M group was subjected to an additional 1.7 x 10(-6) M propranol and 2 mM verapamil infusions for a further 15 min. RESULTS: LAP, PAP, Qp, and Rp were significantly higher in the PHT control group (P<0.001). VIP 10(-5) M increased MAP and decreased PAP significantly with respect to isoproteronol and VIP 10(-6) M (P<0.05). VIP 10(-5) M also decreased Rp significantly in the early post CPB 15th minute (P<0.05), but did not show any superiority to other agents in the following minutes. Verapamil inhibited VIP 10(-5) M effects but propranol did not. CONCLUSION: VIP has dose responsive, positive inotropic and pulmonary vasodilatory effects in whole body CPB model acting via calcium channels.

Adrenergic beta-Agonists↗