Tetsuya Ueno

Spinal cord protection: Development of a paraplegia-preventive solution

We present a clinically available method to protect the spinal cord against ischemic or reperfusion injury and to prevent paraplegia after cross-clamping of the aorta. We separated 35 rabbits into five equal groups and clamped each animals abdominal aorta distal to the left renal artery. We also occluded the aortas 2 cm above the iliac bifurcation for 45 minutes with inflated 5F balloon catheters. Through the catheter port distal to each balloon one of four different solutions was infused at 3 degrees C for 3 minutes at a rate of 5 mL/min (group I, uninfused control; group II, lactated Ringers solution; group III, lactated Ringers solution + 30 mg/kg of methylprednisolone; group IV, lactated Ringers solution+methylprednisolone + 3 mL of 20% mannitol; group V, lactated Ringers solution+methylprednisolone+mannitol + 10 mg/kg of vitamins E and C). We assessed the neurologic status of the hind limbs on the second postoperative day using Tarlovs criteria. The neurologic status in groups III, IV, and V was significantly superior to that of group I (p < 0.05, groups III versus I; p < 0.01, groups IV and V versus I). Spastic paraplegia occurred in 71% of group I, in 43% of group II, in 29% of group III, in 14% of group IV, and not at all in group V. The infusion of our specially blended solution with several spinal cord neuroprotective properties (hypothermia, methylprednisolone, mannitol, and vitamins E and C) achieved the best spinal cord protection against ischemic or reperfusion injury and prevented postoperative paraplegia.

Ulinastatin attenuates reperfusion injury in the isolated blood-perfused rabbit heart

BACKGROUND Ventricular dysfunction after long cardioplegic arrest has been observed in cardiac operations. Urinary trypsin inhibitor, also called ulinastatin, may attenuate myocardial ischemia-reperfusion injury. The present study was designed to determine the protective efficacy of ulinastatin in blood-perfused parabiotic isolated rabbit hearts as a surgically relevant model with long (4-hour) cardioplegic arrest. METHODS Each isolated rabbit heart, with a latex balloon inserted in the left ventricle, was parabiotically blood-perfused using a modified Langendorff column. The left ventricular developed pressure, rate of pressure development, and coronary flow with a left ventricular end-diastolic pressure of 10 mm Hg were measured before ischemia and 15, 30, 45, and 60 minutes after reperfusion began (control, n = 10). Ulinastatin (15,000 U/kg) was administered to the support animal just before reperfusion began (group U-1, n = 10) or at the beginning of the extracorporeal circulation and readministered before reperfusion (group U-2, n = 10). The endothelium of the coronary artery was observed by scanning electron microscopy to evaluate the extent of endothelial ischemia-reperfusion injury. RESULTS Ulinastatin enhanced the recovery of developed pressure in both the U-1 (p<0.05) and U-2 (p < 0.01) groups compared with the control group. Although ulinastatin given just before reperfusion (group U-1) did not enhance the recovery of the rate of pressure development or the coronary flow compared with the control, earlier administration did improve the recovery of the rate of pressure development compared with the control (U-2, p<0.05), and there was improvement of the recovery of coronary flow after 60 minutes of reperfusion (U-2, p<0.05). Scanning electron microscopy showed that ulinastatin had ameliorated coronary endothelial damage. CONCLUSIONS Ulinastatin improved functional recovery after long cardioplegic arrest and reduced coronary endothelial injury. Administration of ulinastatin at the beginning of cardiopulmonary bypass and just before reperfusion may be useful clinically in cases requiring prolonged aortic cross-clamping.

COMPARATIVE HEMOLYSIS STUDY OF CLINICALLY AVAILABLE CENTRIFUGAL PUMPS

Centrifugal pumps have become important devices for cardiopulmonary bypass and circulatory assistance. Five types of centrifugal pumps are clinically available in Japan. To evaluate the blood trauma caused by centrifugal pumps, a comparative hemolysis study was performed under identical conditions. In vitro hemolysis test circuits were constructed to operate the BioMedicus BP-80 (Medtronic, BioMedicus), Sams Delphin (Sarns/3M Healthcare), Isoflow (St. Jude Medical [SJM]), HPM-15 (Nikkiso), and Capiox CX-SP45 (Terumo). The hemolysis test loop consisted of two 1.5 m lengths of polyvinyl chloride tubing with a 3/8 -inch internal diameter, a reservoir with a sampling port, and a pump head. All pumps were set to flow at 6 L/min against the total pressure head of 120 mm Hg. Experiments were conducted simultaneously for 6 h at room temperature (21o C) with fresh bovine blood. Blood samples for plasma-free hemoglobin testing were taken, and the change in temperature at the pump outlet port was measured during the experiment. The mean pump rotational speeds were 1,570, 1,374, 1,438, 1,944, and 1,296 rpm, and the normalized indexes of hemolysis were 0.00070, 0.00745, 0.00096, 0.00066, 0.00090 g/100 L for the BP-80, Sarns, SJM, Nikkiso, and Terumo pumps, respectively. The change in temperature at the pump outlet port was the least for the Nikkiso pump (1.8o C) and the most with the SJM pump (3.8o C). This study showed that there is no relationship between the pump rotational speed (rpm) and the normalized index of hemolysis in 5 types of centrifugal pumps. The pump design and number of impellers could be more notable factors in blood damage.

Protection against ischemic spinal cord injury: One-shot perfusion cooling and percutaneous topical cooling

PURPOSE We investigated the protective effect of two methods of hypothermia against ischemic spinal cord injury: one-shot perfusion cooling and percutaneous topical cooling. METHODS Twenty-five rabbits were divided into five equal groups. The abdominal aorta was isolated proximally by a vascular clamp and distally by an inflated balloon catheter for 60 minutes. Group I served as control. In groups II (2.5 ml/min) and III (5.0 ml/min), hypothermic lactated Ringers solution was infused for 3 minutes from the distal end of the catheter. Ice blocks were placed behind the backs of rabbits 30 minutes before ischemia in group IV. Group V underwent the procedures combined with those in groups II and IV (infusion of hypothermic solution plus placement of ice blocks). Another 15 rabbits underwent laminectomy at the L2 or L3 level. A temperature probe was inserted into the spinal cord to monitor cord temperature continuously during the procedures in all five groups (three rabbits per group). RESULTS Neurologic status on the second postoperative day in groups IV and V was significantly superior to that in group I (p < 0.01), but the neurologic status of groups II and III did not differ significantly from the neurologic status of group I. The spinal cord temperature in groups II and III dropped rapidly with the infusion, but it rose again quickly. In contrast, the spinal cord was kept sufficiently hypothermic during ischemia in groups IV and V. CONCLUSIONS We concluded that the percutaneous cooling method can keep the spinal cord sufficiently hypothermic during ischemia to lead to a significantly superior neurologic outcome.

Unique circulatory responses to exogenous catecholamines after brain death

BACKGROUND For better management of brain-dead donors, we developed a small animal model of brain death. We investigated how three catecholamines commonly used for the management of donors affected the cardiac function, hemodynamics, and tissue blood flow in the endocardium and renal cortex. METHODS Thirty-two rabbits were divided into four groups. Group C served as a control. In group D, dopamine 10 microg/kg/min was infused from 15 to 180 min after brain death. Norepinephrine in group N and epinephrine in group A were infused at 0.5 microg/kg/min. Heart rate, mean arterial pressure, left ventricular developed pressure, left ventricular end-diastolic pressure (LVEDP), LV dP/dt, -peak dP/dt, endocardial flow, renal cortical flow, and their percent changes until 180 min after brain death were compared. RESULTS Acute induction of brain death caused sudden but transient hyperdynamic conditions, followed by profound circulatory collapse. Dopamine and norepinephrine increased heart rate, blood pressure, and endocardial flow at the expense of a reduction in renal cortical flow and had little effect on the other variables. Epinephrine significantly increased all these variables, with the exception of left ventricular end-diastolic pressure and -peak dP/dt, without a corresponding reduction in renal cortical flow. CONCLUSIONS Dopamine and norepinephrine impaired renal perfusion and may reduce the viability of renal grafts before retrieval. Epinephrine improved circulatory collapse and pump dysfunction after brain death, while simultaneously maintaining renal perfusion. We conclude that epinephrine should be selected as the catecholamine of choice for the management of brain-dead donors.

The Impact of Ischaemic Preconditioning on Spinal Cord Blood Flow and Paraplegia

PURPOSE We investigated the effect of ischaemic preconditioning (IP) on ischaemic spinal cord injury in a rabbit model. METHODS Fourteen rabbits were divided into IP and control groups of seven rabbits each. We repeated 3-min clamping of the infrarenal abdominal aorta and 3-min reperfusion twice (preconditioning), followed by 15 min clamping in the IP group. In the control group, the aorta was clamped for 15 min without preconditioning. Lumbar cord blood flow and systemic blood pressure were measured until 3 h of reperfusion. Another 14 rabbits underwent the same procedures with or without IP and neurologic status was assessed on the second postoperative day. RESULTS The percent change in lumbar cord blood flow after reperfusion was significantly greater (P=0.013) in the IP group despite lower mean blood pressure. There was no significant difference in overall neurologic status (P=0.461) but the incidence of spastic paraplegia in the IP group was lower (14%, 1/7) than that of control group (43%, 3/7). CONCLUSION IP increased postischaemic lumbar cord blood flow and contributed to lower incidence of spastic paraplegia.

Protection against Spinal Cord Ischaemia: One-Shot Infusion of Hypothermic Solution

The protective effect of a one-shot infusion of a range of low-temperature hypothermic solutions against spinal cord ischaemia was investigated. Forty rabbits were allocated into five groups each of eight animals. The abdominal aorta of each rabbit was clamped distal to the left renal artery, and also occluded for 30 min above the iliac bifurcation with an inflated 50-gauge French balloon catheter. Ringers solution with lactate was infused through the catheter port distal to the balloon, at various temperatures (group I, uninfused control; group II, 33°C; group III, 23°C; group IV. 13°C; and group V. 3°C). The neurological status of the hind limbs was assessed on the second postoperative day using the criteria of Tarlov. A further eight rabbits underwent laminectomy at L2 or L3. Temperature probes were inserted into the spinal cord and the cord temperature monitored continuously during infusion in four rabbits from each of groups I and V. Spastic paraplegia occurred in five rabbits in group I, three in group II, and two in group III. Four rabbits in groups II and III, seven in group IV and all eight in group V showed complete recovery of neurological function. The infusion of 3°C solution achieved significantly lower spinal cord temperatures in group V after aortic clamping, compared with the temperatures in group I (P< 0.001–0.005). It was concluded that protection against spinal cord ischaemia and prevention of postoperative paraplegia are promoted as the temperature of the hypothermic infusion solution is lowered.

Vasodilator Resistant Lethal Spasm after Uncomplicated Off-Pump Coronary Surgery

We report a case of lethal spasm of non-grafted coronary arteries after an uncomplicated off-pump coronary artery bypass grafting in a patient with no predisposing factors other than smoking. Transcatheter intraluminal injection of several vasodilators failed to relieve the spasm. The patient remained in profound cardiogenic shock due to broad acute myocardial infarction and died of multiple organ failure.

Effect of gradual reperfusion on ventricular function after 6-h preservation.

This experiment was designed to determine the effect of a gradual increase in reperfusion pressure on ventricular function after 6-h preservation of the heart. Twenty-four rabbit hearts were allocated to four groups, each reperfused at different pressures: group I (80mmHg); group II (40mmHg for 10min, then increased to 80mmHg); group III (20mmHg for 5min, then increased by 20mmHg at 5-min intervals); and group IV (as group III + perfusion with recombinant human superoxide dismutase). The developed pressures at balloon volumes of 1.2, 1.5 and 1.8 ml were significantly higher in groups III and IV than in group I. The values of left ventricular peak dP/dt were significantly greater in groups II, III, and IV than in group I. Light microscopical examination revealed severe interstital oedema in group I, moderate oedema in group II, and minimal oedema in groups III and IV. Gradual reperfusion resulted in significantly better systolic function and less interstitial oedema. Use of recombinant human superoxide dismutase provided little additional benefit when combined with gradual reperfusion.

Ruptured pseudoaneurysm of the aorta with encapsulated mediastinal abscess after coronary artery bypass grafting

Rupture of pseudoaneurysm of the aorta with chronic active mediastinitis after cardiac surgery is a catastrophic complication. We report a case of one-stage operation of urgent repair for ruptured pseudoaneurysm under deep hypothermic circulatory arrest, debridement of mediastinum, and omental transfer, with an uneventful postoperative course.