Jerry Gelineau

Autoregulation of spinal cord blood flow: is the cord a microcosm of the brain?

The autoregulatory capability of regional areas of the brain and spinal cord was demonstrated in 18 rats anesthetized with a continuous infusion of intravenous pentothal. Blood flow was measured by the injection of radioactive microspheres (Co57, Sn113, Ru103, Sc46). Blood flow measurements were made at varying levels of mean arterial pressure (MAP) which was altered by neosynephrine to raise MAP or trimethaphan to lower MAP. Autoregulation of the spinal cord mirrored that of the brain, with an autoregulatory range of 60 to 120 mm Hg for both tissues. Within this range, cerebral blood flow (CBF) was 59.2 +/- 3.2 ml/100 g/min (SEM) and spinal cord blood flow (SCBF) was 61.1 +/- 3.6. There was no significant difference in CBF and SCBF in the autoregulatory range. Autoregulation was also demonstrated regionally in the left cortex, right cortex, brainstem, thalamus, cerebellum, hippocampus and cervical, thoracic and lumbar cord. This data provides a coherent reference point in establishing autoregulatory curves under barbiturate anesthesia. Further investigation of the effects of other anesthetic agents on autoregulation of the spinal cord is needed. It is possible that intraspinal cord compliance, like intracranial compliance, might be adversely affected by the effects of anesthetics on autoregulation.

Twelve-hour canine heart preservation with a simple, portable hypothermic organ perfusion device

BACKGROUND Cardiac transplantation is limited to an ischemic time of around 6 hours by available preservation solution and technique. Complex organ preservation devices have been developed that extend this time to 24 hours or more, but are clinically impractical. This study evaluates a portable oxygen-driven organ perfusion device weighing approximately 13.5 kg. METHODS Organs are perfused with the University of Wisconsin solution at low perfusion pressure using less than 400 L of oxygen per 12 hours. Left ventricular parameters were measured in anesthetized adult beagles to establish control values (n = 5). Hearts were procured after cardioplegia with 4 degrees C University of Wisconsin solution, weighed, then stored for 12 hours in University of Wisconsin solution at 4 degrees C. Hearts were perfused (n = 3) or nonperfused (n = 2) during storage. Organ temperature, partial pressure of oxygen in the aorta and right atrium, perfusion pressure, and aortic flow were recorded hourly in perfused hearts. After 12 hours, hearts were transplanted into littermates and left ventricular parameters measured after stabilization off bypass. RESULTS Organ weight for both groups was unchanged. Nonperfused hearts required both pump and pharmacologic support with significantly depressed left ventricular function. Perfused hearts needed minimal pharmacologic support, with left ventricular end-diastolic pressure, cardiac output, and rate of change of left ventricular pressure showing no statistical difference from control. CONCLUSIONS These findings confirm the potential for extended metabolic support for ischemia-intolerant organs in a small, lightweight, easily portable preservation system.

Tracheal gas insufflation combined with high-frequency oscillatory ventilation

OBJECTIVES To determine the efficacy of tracheal insufflation delivered by two different catheter designs on CO2 elimination when used in conjunction with high-frequency oscillatory ventilation. DESIGN A nonrandomized before and after trial. Each animal served as his own control. SUBJECTS Ten mongrel dogs weighing 20.9 +/- 1.9 kg. Four animals were assigned to a normal lung group and six animals underwent lung injury by large volume saline lavage. INTERVENTION Permissive hypercapnia was allowed to occur by selecting oscillator settings that would lead to alveolar hypoventilation. Proximal mean airway pressure was kept constant. Tracheal gas was insufflated at 1 cm above the carina for 30 min periods at gas flows of 5 to 15 L/min. MEASUREMENTS AND MAIN RESULTS Carinal pressure, hemodynamic parameters (cardiac output, mean arterial pressure, pulmonary artery occlusion pressure), and gas exchange parameters (PaCO2, PaO2, PaO2/FIO2, shunt fraction, D O2) were measured. For the normal dogs, at catheter flow of 15 L/min; the forward thrust catheter increased carinal pressure and Pao2/FIO2 BY 30% (p<.003) and 105% (p<.005), respectively. The forward thrust catheter reduced Paco2 by 40% (p<.04). The reverse thrust catheter increased PaO2/FIO2 by 102% (p<.001) and decreased pressure and PaCO2 by 44% (p<.001) and 34% (p<.003), respectively. For the injured dogs, at catheter flow rate of 15 L/min, the forward thrust catheter increased carinal pressure, PaO2, and PaO2/FIO2 by 6% (p<.001), 23% (p<.001), and 24% (p<.02), respectively. The forward thrust catheter reduced PaCO2 by 29% (p<.002). The reverse thrust catheter increased PaO2 and PaO2/FIO2 both by 11% (p<.02) and reduced carinal pressure and PaCO2 by 23% (p<.001) and 18% (p<.002), respectively. CONCLUSIONS Tracheal gas insufflation is capable of improving oxygenation and ventilation in acute lung injury when combined with high-frequency oscillatory ventilation. The addition of this second gas flow at the level of the carina raises or lowers distal airway pressure, the magnitude of which is dependent on the direction and rate of gas flow. The beneficial effects of tracheal gas insufflation may be tempered by the long-term effects of altering distal airway pressure; lowering distal airway pressure may lead to atelectasis, whereas raising distal airway pressure may lead to an auto-positive end-expiratory pressure (auto-PEEP) effect.

Long-term transtracheal high frequency ventilation in dogs

Long-term effects of high frequency percutaneous transtracheal ventilation (HFTV) have not been studied. The purpose of this study is to evaluate the cardiopulmonary effects of 24 h of transtracheal ventilation in dogs at a respiratory rate of 100/min.Four dogs were anesthetized with intermittent pentobarbital and paralyzed with pancuronium. Ventilation in the supine position was through a 14-gauge Angiocath introduced into the trachea through the cricothyroid membrane. A respiratory rate of 100/min was used at an Fio2 of 0.4 using a fluidic logic controlled ventilator. The inspiratory-expiratory ratio was 1:2 and tidal volume 70 ml. The driving pressure of the air-oxygen mixture was 50 psi. After 24 h, residual muscle relaxant was reversed and the animal allowed to recover.There was no significant change in the following parameters over 24 h compared to starting values: Pao2, Paco2, pH, aortic, central venous, pulmonary artery and pulmonary artery wedge pressures, heart rate, cardiac index (CI), stroke index (SI), left ventricular stroke work (LVSW), systemic vascular resistance (SVR), pulmonary vascular resistance (PVR), C(a)o2, oxygen consumption (Vo2), pulmonary shunt (Qs/Qt). A PEEP effect of 2.9–5.0 torr was maintained. All dogs recovered uneventfully. Three days after the experiment, blood gases of 2 dogs were normal. One dog was killed after 3 days; macroscopic and microscopic examinations of the upper and lower airway and pulmonary parenchyma were normal.Dogs can be ventilated for as long as 24 h using HFTV transtracheally at rates of 100/min without adverse cardiopulmonary effects.

Cognitive performance and cerebrohemodynamics associated with the Persian Gulf Syndrome

The Persian Gulf Syndrome generally manifests as a set of nonspecific complaints with emphasis on central nervous system impairment. The purpose of this study was to determine if cognitive performance and middle cerebral artery blood flow velocity (MCABFV) were altered in symptomatic Gulf War veterans (sGWVs) and asymptomatic Gulf War veterans (aGWVs) by exposure to low levels of acetone. MCABFV was assessed in male aGWVs (n=8) and sGWVs (n=8) during cognitive challenges while breathing 1) clean air, 2) a clean air placebo, and 3) a mixture of air and 40 parts per million (ppm) acetone. Pulmonary function was also evaluated. Pulmonary function tests showed no statistical differences between aGWVs and sGWVs while breathing clean air or 40 ppm acetone in air. Cognitive performance was similar during the clean air, placebo, and acetone test conditions for sGWVs and aGWVs. Data pooled across test conditions for each group indicated a statistically significant (P <0.05) poorer performance primarily in memory and executive function tasks by sGWVs. sGWVs had a 34.2% higher baseline MCABFV than aGWVs (P <0.05). Increases in MCABFV for aGWVs (averaged over all cognitive tasks for each test condition) ranged between 7.8% and 8.8%, and were not statistically significant. Increases for sGWVs ranged between 0.3% and 4.8%, averaged over all cognitive tasks for each test condition. No significant differences were noted between the clean air and placebo test conditions but both were significantly different compared to the acetone condition. Differences in MCABFV increases for each of the test conditions between aGWVs and sGWVs were also statistically significant. sGWV did not appear to demonstrate pulmonary dysfunction following exposure to acetone. They did, however, appear to have generally lower cognitive function as compared to aGWVs. sGWVs appeared to have a significant degree of autoregulatory disruption in cerebral perfusion, resulting in reduced cognitive reserve capacity and potentially impaired ability to handle complex cognitive tasks.

Oxygen consumption during oxygenated hypothermic perfusion as a measure of donor organ viability.

Hypothermic machine perfusion (HMP) for the preservation of kidneys, recovered from extended criteria organ donors (ECDs), presents the opportunity for assessing ex vivo parameters that may have value in predicting postimplantation organ viability. Organ perfusion and vascular resistance are the parameters most frequently cited as the basis for the decision to use or discard a donor kidney. The limitation of these measures is emphasized by the observation that a significant percentage of ECD kidneys with poor perfusion parameters can provide life-sustaining function after transplantation. It has been suggested that whole organ oxygen consumption (OC) during oxygenated HMP may better reflect the proportion of viable tissue in the organ and more reliably predict posttransplant organ function. Our study correlates renal OC and renal vascular resistance (RVR) during oxygenated HMP with postpreservation glomerular filtration rates (GFRs) in rodent kidneys after 24 hours of oxygenated HMP. Kidneys from adult rodents were preserved for 24 hours using oxygenated HMP and static cold storage (SCS). During oxygenated HMP preservation, organ OC, renal organ flow rates, and RVR were serially measured. After the preservation period, organs were mounted onto a Langendorff device for warming to normal body temperature and measurement of GFR. Oxygen consumption and RVR during HMP were correlated with postpreservation GFR. Oxygen consumption during oxygenated HMP was significantly correlated (r2 =0.871; p < 0.05) with postpreservation GFR, suggesting that higher OC predicts better postpreservation GFR. In contrast, RVR was poorly correlated with postpreservation GFR (r2 =0.258; p = 0.199). Glomerular filtration rate in SCS kidneys was 0.002 ± 0.003 ml/min/g. We demonstrate that measurement of organ OC during oxygenated HMP may have significant value in predicting postpreservation organ function.

Perfusion preservation of rodent kidneys in a portable preservation device based on fluidics technology

Background. Technology that can implement the basic requirements for successful organ preservation in a portable configuration has yet to be realized. Methods. This work evaluates kidney preservation in a new class of portable organ preservation technology based on fluidics principles. During hypothermic pulsatile perfusion preservation (HPPP), oxygen consumption, renal vascular resistance (RVR), pH, pCO2, and perfusion pressure were measured. After 24 hr of preservation, perfusate distribution was assessed, and oxygen consumption, RVR, and glomerular filtration rate (GFR) were compared in perfused, statically stored, and freshly harvested kidneys. Results. During HPPP, perfusion pressure was 5.8±3.3 mmHg with oxygen delivery to the organs in excess of 3.5 times the organ metabolic requirement. During function measurements, RVR was not statistically different in the three groups; however, both oxygen consumption and GFR in the statically stored organs were significantly lower than in HPPP stored or freshly harvested kidneys. Conclusions. Our findings suggest that full portability in a hypothermic perfusion preservation device seems feasible utilizing fluidics-based technology.

Continuous‐flow apneic ventilation with small endobronchial catheters

This study compares gas exchange and hemodynamic parameters during bronchial insufflation with two different internal diameter (ID) catheters (2.5 and 1.4 mm) at a constant mean gas exit velocity. Anesthetized, paralyzed dogs were instrumented to monitor arterial, central venous, and airway pressures, blood gases, temperature, ECG, and ventilated using continuous flow apneic ventilation (CFAV) via 2.5‐mm or 1.4‐mm ID bronchial insufflation cathethers positioned 1.25 bronchial diameter units (BDU) beyond the carina. Initially, flow was adjusted to provide adequate oxygenation and ventilation through the 2.5‐mm ID catheters. After a 30‐min stabilization, physiological parameters were recorded and the mean gas exit velocity was calculated. The 2.5‐mm ID insufflation catheters were then replaced by 1.4‐mm ID catheters and the bronchial insufflation flow adjusted so as to produce the same mean gas exit velocity as for the 2.5‐mm ID catheters. After a 30‐min stabilization period, physiological parameters were again recorded. No significant differences were noted in arterial, central venous, or airway pressures, temperature, heart rate, pH, Paco2, and Pao2 between the 2.5‐mm and 1.4‐mm ID bronchial insufflation catheters. However, significantly less bronchial insufflation flow (69.7%) was required to maintain oxygenation and ventilation for the 1.4‐mm ID bronchial insufflation catheters.

ICP and CBF Reactivity to Isoflurane and Nitrous Oxide During Normocarbia, Hypocarbia and Intracranial Hypertension

The search for an inhalational agent that does not adversely affect cerebrovascular dynamics has been stimulated by the realization that nitrous oxide, halothane and enflurane share the common properties of being potent cerebral vasodilators and affecting cerebral metabolism. Thus, in the face of intracranial dysfunction, these agents may uncouple flow from metabolism; markedly change intracranial compliance; modify CSF flow characteristics by changing outflow resistances, production and absorption; and challenge autoregulation. Enflurane has the added ability of being epileptogenic, especially during hypocapnia.

Method for three-dimensional visualization of neurodegeneration in cupric-silver stained serial rat brain slices

The spatial distribution of neurodegeneration in brains is difficult to visualize when working from 2-D serial slices. In studies where repetitive operant behavior measurements are made over several weeks following organic solvent exposure, definitive evidence of degeneration in brain structures may have been significantly cleared by the time the tissue is prepared histologically. The only remaining evidence that injury has occurred may be nothing more than neuronal and cellular debris. By choosing stains that are specific for this type of residual and/or indicative of specific pathology, a 3-D representation of the spatial distribution of the neuronal and cellular debris fields within the organ can be highlighted and displayed. We present a method for visualizing the spatial distribution of neuronal degeneration that can result from low-level organic solvent exposure scenarios. A cupric-silver stain highly specific for neuronal degeneration is used to identify neuronal debris fields in 73 serial slices of brains of rodents that were exposed to toluene vapors. Serial brain sections stained with cupric-silver are scanned at 600 dpi using a gray-scale protocol. Using commercially available software, scans are assembled into 3-D images showing both topographical and internal anatomical details. The reassembled images are further processed into stereo pairs. Gray-scale scans are compared to the original sections to establish gray-scale ranges for healthy and damaged tissue and artifact staining.