Retrograde transvenous neuroperfusion: a back door treatment for stroke.

BACKGROUND AND PURPOSE: Stroke is the third leading cause of death and the leading cause of adult disability in the United States. The clot-lysis drug tissue plasminogen activator is the only treatment that has been effective for acute stroke patients, yet there are significant limitations to its use and effectiveness. In this study retrograde transvenous neuroperfusion (RTN) was evaluated for its efficacy in reversing acute ischemia, preventing paralysis, and limiting pathological evidence of infarction in baboons. METHODS: Ten adult male baboons underwent 3.5 hours of reversible middle cerebral artery occlusion (MCAO) under isoflurane (0.25% to 1.5%) anesthesia. Five randomly chosen animals received RTN treatment 1 hour after start of MCAO. Somatosensory evoked potentials were recorded during MCAO. Animals were assigned daily neurological scores. Animals were killed 6 days after MCAO, and brains were quantitatively analyzed for infarct volume. RESULTS: Within 1 hour after RTN was started, treated animals showed significantly improved somatosensory evoked potentials (103.3% versus 75% of baseline; P<0.01). Likewise, the combined neurological score for the RTN-treated group was 99.2, while the combined mean score for the untreated group was 66.4 (P<0.015). The mean infarction volume was 8.8+/-3.1% (of contralateral hemisphere) for the control group and 0.3+/-0.2% for the RTN-treated group (P<0.01). No increased mortality was seen in the RTN-treated group. CONCLUSIONS: We conclude that RTN treatment during MCAO effectively reverses the pathophysiological sequelae of ischemia, even when the treatment is initiated 1 hour after the onset of ischemia. Although the infarct volume in the control group was variable when quantitatively assessed 6 days after 3.5 hours of MCAO, virtually no evidence of infarcts was seen in the RTN-treated group.

Isolated limb thrombolysis with extracorporeal pump and urokinase.

In order to determine the effect of altering the method of delivery of lytic therapy, both hind limbs of 55 adult mongrel dogs were embolized to occlusion and divided into six different treatment groups. Each right limb received 100,000 units of urokinase (UK) intraarterially by one of six different treatment protocols: Group I (n = 10), 5-min infusion with control of arterial inflow (IC); Group II (n = 10), 5-min infusion without IC; Group III (n = 10), 30-min infusion with IC; Group IV (n = 10), 30-min infusion without IC (simulates percutaneous infusion); Group V (n = 10), isolated limb perfusion (ILP) with femoral arterial and venous cannulation and proximal tourniquet control using an extracorporeal circulating pump at a controlled rate and constant temperature (37 degrees C) for 30 min; Group VI (n = 5), underwent ILP without urokinase. A morphometric score was used to quantitate angiographic changes. Films were compared before and after treatment and the net difference for each animal was recorded. [table: see text] We conclude that maintenance of blood flow during urokinase infusion enhances its effectiveness and, contrary to previous recommendations, during intraoperative delivery, inflow should be maintained. Isolated limb perfusion alone was as effective as a 30-min infusion of urokinase without inflow control. Isolated limb perfusion plus UK was by far the most effective method of administering lytic therapy. These experiments suggest that the mechanical action of flowing blood enhances clot dissolution and significantly increases the effectiveness of pharmacologic lysis. Isolated limb fibrinolytic perfusion may have clinical potential in the surgical treatment of limb ischemia.

Pulmonary edema and fluid mobilization as determinants of the duration of ECMO support.

The physiological variables that govern recovery of pulmonary function during neonatal extracorporeal membrane oxygenation (ECMO) remain poorly understood. We hypothesized that pulmonary hypertension (PHN) resolves soon after starting ECMO and that neonatal weight gain, pulmonary edema, and fluid mobilization are major determinants of recovery of pulmonary function and the ability to decrease ECMO support. To evaluate this, 17 consecutive neonates requiring ECMO for severe respiratory failure were reviewed. PHN was studied by daily echocardiography to assess the direction of ductal shunting. To evaluate fluid flux, pulmonary function, and edema during ECMO, we measured body weight, urine output, and ECMO flow every 12 hours. To evaluate pulmonary edema, serial chest radiographs obtained every 12 hours were randomly reviewed and scored by two radiologists with a semiquantitative chest radiograph index score (CRIS). By 25% of bypass time, PHN had resolved in all patients. However, at that time, weight had increased to 9.16% +/- 1.78% above birth weight, and the CRIS was 44% worse than the value just prior to ECMO. From 25% time on bypass, as urine output increased, patient weight and CRIS progressively decreased, allowing ECMO support to be weaned. At the time of discontinuation of ECMO support, weight had decreased to 2.0% +/- 1.3% above birth weight, and urine output remained steady at 3.0 +/- 0.3 mL/kg/h. Within 24 hours of stopping ECMO, the CRIS showed a 58% improvement compared to maximal scores during ECMO. We conclude that PHN decreases early in ECMO and that edema and its mobilization are important determinants of the improvement in pulmonary function and duration of ECMO.(ABSTRACT TRUNCATED AT 250 WORDS)

Reduction of operative heat loss and pulmonary secretions in neonates by use of heated and humidified anesthetic gases.

Maintaining normothermia in neonates undergoing major operations remains a serious problem which may complicate the perioperative period. During the past 5 years at the UCLA Hospital, 86 infants have undergone general anesthesia for repair of congenital malformations. Heated, humidified ventilation (HHV) was used in 48 neonates and standard ventilation (SV)--that is, dry anesthetic gases--was used in the other 38. We found that loss of body heat during the period of anesthesia was significantly less when HHV was used. The mean rectal temperature of HHV infants decreased 0.2 degrees C during the first hour of anesthesia, whereas the mean temperature decreased 1.4 degrees C in SV infants (p < 0.01). By the end of anesthesia, the mean temperature of HHV infants had increased 0.3 degrees C, whereas in SV infants the mean temperature was 1.2 degrees C lower than at the beginning of anesthesia (p < 0.01). Furthermore, postoperative atelectasis was less frequent in HHV patients (three cases) than in SV infants (nine cases), and pulmonary secretions were less voluminous and tenacious in neonates receiving heated humidified anesthetic gases, although objective quantification of these observations was not done. Inasmuch as no complications were observed in any of the 48 neonates receiving HHV, and previous studies showed that HHV does not interfere with anesthetic gas uptake, it appears that HHV may be a useful adjunct to the currently used methods of neonatal anesthesia.