Mitsuya Murase

Retrograde cerebral perfusion through a superior vena caval cannula protects the brain

Retrograde cerebral perfusion through a superior vena caval cannula is a new technique for protecting the brain during aortic arch operations. In mongrel dogs (n = 10; 13 to 15 kg) we have performed retrograde cerebral perfusion (300 mL/min) by infusing blood through a superior vena caval cannula with aortic and inferior vena caval drainage. We have measured the cerebral tissue blood flow, oxygen consumption, and carbon dioxide exudation during retrograde cerebral perfusion at normothermia (NT, 37 degrees C) and hypothermia (HT, 20 degrees C) and have compared these values with values obtained in dogs during cardiopulmonary bypass (1,200 mL/min). Cerebral tissue blood flow was measured by the hydrogen clearance method. During retrograde cerebral perfusion about 20% of the superior vena caval perfusate was returned through the aorta and the rest drained from the inferior vena cava. Cerebral vascular resistance during retrograde cerebral perfusion was lower than that during cardiopulmonary bypass (NT, 63.8 +/- 52.5 versus 126.9 +/- 58.4; HT, 28.4 +/- 32.8 versus 69.5 +/- 28.7 x 10(3) dynes.s.cm(-5). Retrograde cerebral perfusion provided half the cerebral tissue blood flow of cardiopulmonary bypass (NT, 14.7 +/- 6.4 versus 34.3 +/- 7.8; HT, 17.6 +/- 5.6 versus 37.2 +/- 10.6 mL/min). Retrograde cerebral perfusion also provided a third of the oxygen (NT, 4.4 +/- 2.1 versus 12.3 +/- 7.1; HT, 1.4 +/- 0.8 versus 4.2 +/- 1.3 mL/min) and discharged 20% of the carbon dioxide (NT, 0.24 +/- 0.08 versus 1.19 +/- 0.58; HT, 0.15 +/- 0.06 versus 0.51 +/- 0.17 mmol/min) when compared with cardiopulmonary bypass. Retrograde cerebral perfusion may reduce ischemic damage during interruption of cerebral blood flow.

Early clinical results of retrograde cerebral perfusion for aortic arch operations in Japan.

BACKGROUND In Japan, retrograde cerebral perfusion (RCP) has been used for protection of the brain since 1986. The techniques vary by institution, and thus the optimum perfusion conditions have not yet been established. METHODS A survey of 49 institutions was performed to investigate the early results of RCP in Japan. There were 228 patients collected, 46 (20.2%) of whom sustained brain complications. Twenty-seven patients had permanent and 19, temporary neurologic dysfunction. There were 31 early deaths (13.6%) and an additional 14 hospital deaths (6.1%). Significant predictors of brain complications and mortality were evaluated by univariate analysis and multivariate analysis using stepwise logistic regression. RESULTS By multivariate analysis, preoperative cardiac arrest (odds ratio 8.901, p = 0.0004) and RCP duration longer than 60 minutes (odds ratio 3.234, p = 0.0352) were significant predictors of permanent neurologic dysfunction. Preoperative hemodynamic compromise (odds ratio 6.150, p = 0.0070), presence of preoperative neurologic symptoms (odds ratio 7.155, p = 0.0283), and left thoracotomy (odds ratio 2.37, p = 0.0335) were significant predictors of early death. Duration of RCP was the single RCP-related factor predictive of a brain complication (odds ratio 1.025 per minute, p < 0.0001). The incidence of permanent neurologic dysfunction was less than 10% when the RCP time was shorter than 60 minutes but increased abruptly when the RCP time exceeded 100 minutes, and it remained approximately 15% between 60 and 99 minutes. CONCLUSIONS Less than 60 minutes of RCP can be tolerated with minimal risk of brain complication. Retrograde cerebral perfusion is one method of cerebral protection during circulatory arrest. This method is not the complete answer for brain protection, but, given specific guidelines, it may help prolong the safe time of circulatory arrest.

Evaluation by pulsed doppler echocardiography of the atrial contribution to left ventricular filling in patients with DDD pacemakers

To evaluate the significance of the left atrial (LA) contribution to left ventricular (LV) filling in cardiac pacing, LV inflow velocity was recorded with pulsed Doppler echocardiography in 20 patients with a DDD pacemaker. The pacemaker was programmed to atrioventricular (AV) sequential pacing with AV intervals of 50, 100, 150, 200 and 250 ms, and then to VVI pacing at a fixed rate of 70 beats/min. To evaluate the relative changes of LV filling volume in individual patients, the percent change in time-velocity integral of LV inflow velocity in each pacing mode was calculated as the ratio to that of AV sequential pacing with an AV interval of 150 ms. To estimate the degree of LA contribution to LV filling, the ratio of time-velocity integral during LA ejection phase to that during total LV filling phase was measured at the optimal AV interval. The percent LV inflow volume in AV sequential pacing was 74% for an AV interval of 50 ms, 87% for 100 ms, 98% for 200 ms and 90% for 250 ms. The percent LV inflow volume in VVI pacing was 72%. The percent LV inflow volume at AV intervals of 150 ms was significantly greater than that at an AV interval of 50, 100 and 250 ms, and in VVI pacing (p less than 0.05). The degree of LA contribution to LV filling showed a positive correlation with the percent increase of LV inflow volume with mode conversion from VVI to AV sequential pacing (p less than 0.005) and also with age (p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Comparative experimental study between retrograde cerebral perfusion and circulatory arrest

To evaluate the efficacy of retrograde cerebral perfusion in protecting the brain, we comparatively studied retrograde cerebral perfusion and total circulatory arrest in 18 hypothermic (20 degrees C) mongrel dogs (retrograde cerebral perfusion, n = 10; total circulatory arrest, n = 8). Retrograde cerebral perfusion was performed, maintaining an external jugular venous pressure of 25 mm Hg for 60 minutes. Retrograde cerebral perfusion provided half the cerebral blood flow and a third of the oxygen that was supplied during hypothermic cardiopulmonary bypass, which had a flow rate of 100 ml/min per kilogram. Oxygen consumption and carbon dioxide exudation did not increase on resuming cardiopulmonary bypass after retrograde cerebral perfusion, whereas they increased after total circulatory arrest (oxygen consumption 10.7 +/- 5.3 versus 19.1 +/- 8.6 ml/min, p < 0.05; carbon dioxide exudation, 0.92 +/- 0.54 versus 1.64 +/- 0.78 mmol/min, p < 0.05). Therefore, oxygen debt during retrograde cerebral perfusion was smaller than during total circulatory arrest. Retrograde cerebral perfusion also cooled the brain better than did total circulatory arrest (20.4 degrees +/- 1.5 degrees C versus 22.7 degrees +/- 0.7 degrees C, p < 0.01). Cerebral tissue oxygen tension decreased slightly (27.5 +/- 7.7 versus 12.3 +/- 3.0 mm Hg, p < 0.01), and cerebral tissue carbon dioxide tension increased slowly during retrograde cerebral perfusion (95 +/- 34 versus 147 +/- 44 mm Hg, p < 0.05). These changes were smaller than those seen in total circulatory arrest. Tissue concentrations of adenosine triphosphate in the brain remained relatively high during retrograde cerebral perfusion but decreased rapidly during total circulatory arrest (0.49 +/- 0.16 versus 0.21 +/- 0.05 mmol/gm, p < 0.01, just before resuming cardiopulmonary bypass). Retrograde cerebral perfusion cannot maintain aerobic metabolism but may reduce ischemic damage of the brain and may safely extend the cerebral circulation interruption time.

Left atrial function after Cox's maze operation concomitant with mitral valve operation

BACKGROUND This study examined whether the atrial fibrillation that commonly occurs in patients with a mitral valve operation could be eliminated by a concomitant maze operation. METHODS Left atrial function after Coxs maze operation performed concomitantly with a mitral valve operation was evaluated in 10 patients ranging in age from 38 to 67 years (mean age, 54 years). Seven patients who had had coronary artery bypass grafting served as the control group. Using transthoracic echocardiography, the ratio between the peak speed of the early filling wave and that of the atrial contraction wave (A/E ratio) and the atrial filling fraction (AFF) were determined from transmitral flow measurements. These two indices have been considered to represent the contribution of left atrial active contraction to ventricular filling. RESULTS The A/E ratio and the AFF were significantly lower in the maze group (0.35 +/- 0.17 versus 0.97 +/- 0.28 [p < 0.01] and 17.6% +/- 8.8% versus 36.8% +/- 6.4% [p < 0.01], respectively). The A/E ratio and the AFF correlated inversely with age (r = -0.72, p < 0.05 and r = 0.76, p < 0.05, respectively) in the maze group. In an angiographic study, the mean left atrial maximal volume index in the maze group was approximately three times larger than that in the control group (117.5 +/- 24.3 mL/m2 versus 35.3 +/- 6.6 mL/m2 [p < 0.01]). The left atrial active emptying volume index was significantly smaller in patients in the maze group (7.2 +/- 2.5 mL/m2 versus 13.1 +/- 4.6 mL/m2 [p < 0.01]). CONCLUSIONS After the maze procedure performed concomitantly with a mitral valve operation in patients with a dilated left atrium, left atrial contraction is detectable but incomplete in the elderly.

Neural tissue-related proteins (NSE, G0α, 28-kDa calbindin-D, S100b and CK-BB) in serum and cerebrospinal fluid after cardiac arrest

To estimate brain damage after cardiac arrest, the concentrations of neuron specific enolase (NSE), GTP-binding protein (G0 alpha), 28 kDa calbindin-D, S100b protein, and creatine kinase BB (CK-BB) in serum and cerebrospinal fluid (CSF) were determined by enzyme immunoassays. Ten mongrel dogs were subjected to 30 min of circulatory arrest at normal body temperature and serial CSF and blood samples were taken during the first 18 h after reperfusion. The NSE concentration in CSF increased significantly after reperfusion, reaching a 15-fold increase (243 +/- 107 ng/ml, p < 0.01) 18 h later, however, it did not increased significantly in serum (8.1 +/- 3.3 ng/ml vs. 23.5 +/- 7.0 ng/ml). G0 alpha concentration in CSF increased sharply between the 2nd and 4th h after reperfusion and peaked 18 h after reperfusion (428 +/- 195 pg/ml, p < 0.01), however, it did not increase significantly in serum. Calbindin-D concentration in CSF increased between the 1st and 6th h after reperfusion, and reached a plateau thereafter (621 +/- 235 ng/ml, a 23-fold increase, p < 0.05) and also increased significantly in serum (p < 0.05). The S100b concentration in CSF also increased dramatically after the 4th h of reperfusion and reached a plateau at the 8th h after reperfusion (16.0 +/- 9.3 ng/ml, a 50-fold increase, p < 0.01), however, it in serum was below the detection threshold. The CK-BB concentration in CSF peaked 4 h after reperfusion (113 +/- 69 ng/ml, a 19-fold increase, p < 0.01) and it in serum increased 4-fold (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Dynamic cardiac compression improves contractile efficiency of the heart

The effect of dynamic cardiac compression on left ventricular contractile efficiency was assessed in terms of the pressure-volume relationship and myocardial oxygen consumption. In 11 excised cross-circulated dog hearts, the ventricle was directly compressed during systole (dynamic cardiac compression). Measurements for pressure-volume area (a measure of total mechanical energy), external work, and myocardial oxygen consumption were done before and during dynamic cardiac compression. Dynamic cardiac compression increased pressure-volume area by 28% +/- 17% (mean plus or minus the standard deviation) and external work by 24% +/- 20% (p = 0.0000185 and 0.0000212, respectively) at given end-diastolic and stroke volumes without affecting myocardial oxygen consumption. As a result, the oxygen cost of pressure-volume area, that is, the slope of the myocardial oxygen consumption-pressure-volume area relationship, significantly decreased by 16% +/- 13% (p = 0.0000135) whereas the pressure-volume area-independent myocardial oxygen consumption was unchanged. Then, contractile efficiency, that is, the reciprocal of the slope of the myocardial oxygen consumption-pressure-volume area relationship in joules significantly improved from 45% +/- 8% to 53% +/- 13% (p = 0.0000437). When the native myocardial oxygen consumption-pressure-volume area relationship was assessed by subtracting the dynamic cardiac compression pressure applied to the heart, the slope of the myocardial oxygen comsumption-pressure-volume area relationship returned to the control level. This indicates that the contractile efficiency of the native heart was not affected by dynamic cardiac compression. We conclude that dynamic cardiac compression enhances left ventricular pump function by improving the contractile efficiency of the overall heart leaving the energetics of the native heart unchanged.

Body temperature influences regional tissue blood flow during retrograde cerebral perfusion

OBJECTIVE This study compared the cerebral microcirculation during retrograde cerebral perfusion with that during antegrade cardiopulmonary bypass under normothermic and hypothermic conditions. METHODS Brain tissue blood flow was measured with the hydrogen-clearance and colored microsphere (15 and 50 microns) methods during antegrade cardiopulmonary bypass and retrograde cerebral perfusion. Measurements were performed during normothermia (37 degrees C), moderate hypothermia (28 degrees C) and deep hypothermia (20 degrees C) in groups of mongrel dogs (n = 8). RESULTS During antegrade cardiopulmonary bypass, the microsphere method showed a significant decrease in cerebral blood flow as body temperature decreased (40.1 +/- 20.8 ml/min/100 gm at 37 degrees C, 16.2 +/- 18.0 ml/min/100 gm at 20 degrees C with 50 microns microspheres) At 20 degrees C, the cerebral blood flow measured with the 15 microns microspheres was significantly lower than that assessed with the hydrogen-clearance method (11.3 +/- 7.0 vs 24.8 +/- 7.0 ml/min/100 gm). During retrograde cerebral perfusion, the microsphere method also showed a significant decrease in cerebral blood flow with cooling. At 37 degrees C, the cerebral blood flow measured with the 15 microns microspheres (0.8 +/- 0.7 ml/min/100 gm) was significantly lower than that assessed with the hydrogen-clearance method (10.1 +/- 3.5 ml/min/100 gm). At both 28 degrees and 20 degrees C, the hydrogen-clearance method showed significantly higher cerebral blood flow (10.1 +/- 5.8 and 8.2 +/- 3.7 ml/min/100 gm) than did the 50 microns microspheres (1.8 +/- 0.6 and 1.0 +/- 0.8 ml/min/100 gm) and 15 microns microspheres (0.23 +/- 0.14 and 0.18 +/- 0.15 ml/min/100 gm). CONCLUSION (1) Cerebral blood flow that shunts to capillaries is increased during antegrade cardiopulmonary bypass under deep hypothermia. (2) During retrograde perfusion, the majority of the blood flow shunts away from brain capillaries, even under normothermic conditions, and blood flow through large venoarterial shunts increases as body temperature decreases. Although the cerebral microcirculation during retrograde perfusion is decreased, retrograde perfusion provides some degree of oxygenation to the body.

Regional cerebral tissue blood flow measured by the colored microsphere method during retrograde cerebral perfusion

Brain tissue blood flow was measured precisely by the colored microsphere method during retrograde cerebral perfusion in 10 normothermic mongrel dogs. The average tissue blood flow rates to the cerebral cortex, cerebral medulla, brain stem, cerebellum, and spinal cord during retrograde cerebral perfusion at 25 mm Hg of external jugular venous pressure were 10.5 +/- 10.3, 4.2 +/- 4.6, 11.1 +/- 9.8, 12.3 +/- 8.6, and 9.1 +/- 5.8 ml/min per 100 gm, respectively. The brain was perfused wholly by retrograde cerebral perfusion without lateralization. Total cerebral blood flow was calculated as the sum total rates of blood flow to each area. Total cerebral blood flow during retrograde cerebral perfusion at 25 mm Hg was 7.8 +/- 4.4 ml/min, which represented 3.5% +/- 1.9% of whole body blood flow and one third of the total cerebral blood flow (28.0 +/- 4.2 ml/min) during cardiopulmonary bypass at a flow rate of 1000 ml/min. Oxygen consumption and carbon dioxide elimination by the total cerebrum during retrograde cerebral perfusion at 25 mm Hg were 0.54 +/- 0.23 ml/min and 34 +/- 15 mumol/min, respectively, or 8.6% +/- 3.6% and 7.0% +/- 3.1% of the corresponding whole body value and represented about one third of that measured during cardiopulmonary bypass (1.21 +/- 0.39 ml/min and 96 +/- 15 mumol/min). Total cerebral blood flow, total cerebral oxygen consumption, and carbon dioxide elimination increased as the external jugular venous pressure increased from 15 to 25 mm Hg; however, no further increase occurred once the external jugular venous pressure exceeded 25 mm Hg.

Role of tyrosine specific phosphorylation of cellular proteins, especially EGF receptor and p125FAK in human lung cancer cells

To clarify the role of tyrosine phosphorylation of cellular proteins in human lung cancer cells, phosphotyrosine (PTYR)-containing proteins in lung cancer cell lines and in paired tissues resected from cancerous and normal lungs were studied by immunoblotting with an anti-PTYR antibody. We found that the profiles of protein phosphorylation were very similar among those cell lines which had different histological features. The major PTYR-containing proteins (180-190 KDa, 120-130 KD, and 95-100 KDa) were detected in lung cancer cell lines. The expression of EGF receptor (EGF-r) (p185) and o-erb B2 protein, and tyrosine phosphorylation of p125FAK were examined in cancerous lung tissues and normal lung tissues. In surgical specimens, approximately half of the samples of lung cancer tissues showed clear elevation of tyrosine phosphorylation. In these cancerous tissues, no clear amplification of EGF-r and c-erb B2 protein expression was observed. However, elevation of tyrosine phosphorylation of p125FAK was observed in cancerous lung tissues but not in normal lung tissues, and its phosphorylation was closely correlated with the nodal involvement of cancer and disease-free survival time. These results suggested that the intracellular signaling pathway via tyrosine phosphorylation plays a role in the generation and immortalization of lung cancer, and assessment of tyrosine phosphorylation of cellular proteins. especially p125FAK, may be available clinically as a prognostic factor.