Anderson, Robert E.

AbstractBackgroundCompelling evidence supports multiple benefits of physical activity (PA) even in small bursts. Less than 50% of Americans achieve recommended PA levels, lower still for individuals living with chronic illness or disease.PurposeThe purpose of this study was to develop and evaluate the feasibility and preliminary effects of 3‐min follow‐along video scenarios to promote brief episodes of low–moderate levels of PA among individuals with chronic diseases.MethodsGuided by our previous studies and self‐efficacy theory, the program (WellMe in 3© for Patients) was modeled after another program developed for healthcare staff. An advisory panel and a health and fitness expert guided the creation of twelve 3‐min video scenarios that included two individuals living with chronic illness and a fitness leader who guided the PA scenarios and how to adapt them based on limitations. The 12 scenarios included 3 min of aerobic activities, stretching, or balance. Preliminary pilot effects were measured among 39 patients living with chronic conditions for one month. Standardized instruments were used to measure PA levels, PA self‐efficacy (SE), and quality of life (QoL); usability and satisfaction were assessed using researcher‐developed tools. Descriptive and inferential statistics were used to evaluate change over time.ResultsTwelve video scenarios were created tailored to persons with chronic illness. Thirty‐nine participants piloted the program, reporting an average of two chronic conditions. Baseline QoL scores were lower than normative data, self‐efficacy scores were low‐to‐moderate, and PA levels were very low. Participants averaged using one video per day. 62% of participants provided complete self‐reported pre‐ and post‐QoL and SE data and 41% provided pre‐ and post‐PA (accelerometer) data. Significant improvements were found for general health and energy scores, and trends were found for self‐efficacy scores. PA levels were highly variable with nonsignificant increases from baseline. Effect sizes were low–moderate for several measures. About 79% of participants rated program “Very good”; all recommended the program.Linking Evidence to ActionPhysical activity has multiple health benefits for all people including those living with chronic conditions. Even short bouts of physical activity have health benefits. A program of 3‐min follow‐along PA videoclips for individuals living with chronic disease holds promise for clinicians and researchers.

In vivo panoramic imaging of regional cortical blood flow and intracellular brain pH with umbelliferone fluorescence was performed in fasted New Zealand White rabbits (n = 30) subjected to constant or stepwise increases in arterial PCO2 (PaCO2) up to 160 mmHg under 1.0% halothane anesthesia. At a PaCO2 of 40 mmHg, baseline brain pHi measured 7.03 +/- 0.04, while regional cortical blood flow was 47.0 +/- 4.3 ml.100 g-1.min-1. With an immediate but constant exposure to a PaCO2 of 60, 80, or 120 mmHg, at 15 min pHi fell to 6.94 +/- 0.03, 6.89 +/- 0.03, and 6.90 +/- 0.03 and recovered over 20, 80, and 120 min, respectively. At 160 mmHg PaCO2, pHi fell to 6.68 +/- 0.04 and remained acidotic. With stepwise increases in PaCO2 up to 80 mmHg, brain pHi decreased from 7.01 +/- 0.02 to 6.99 +/- 0.02, not significantly different despite a severe systemic acidosis of 7.022 +/- 0.034. At a PaCO2 of 120 and 160 mmHg, pHi dropped to 6.97 +/- 0.02 and 6.93 +/- 0.02, respectively. The difference in brain pHi between an immediate and stepwise exposure to a PaCO2 of 160 mmHg was significant (P < 0.005). These results demonstrate that brain pHi is tightly regulated across the cortical surface and resistant to profound changes in extracellular pH. The difference in pHi between the constant and incremental increases in PaCO2 suggests that there is upregulation of pH homeostatic mechanisms.

The effects of nitric oxide synthase inhibition on brain acidosis, regional cortical blood flow (rCBF), and NADH redox state were examined using in vivo fluorescence imaging during four 15-min periods of moderate focal cerebral ischemia, each separated by three 5-min reperfusion periods followed by a final 3-h reperfusion period. Fasted rabbits under 1.5% halothane were divided into six groups of seven animals each: nonischemic controls, ischemic controls, and the following drug groups receiving NG-nitro-L-arginine methyl ester (L-NAME) intravenously 20 min before repetitive ischemia (as follows: 0.1 mg/kg, 1 mg/kg, 10 mg/kg, and 1 mg/kg + 5 mg/kg L-arginine). L-NAME at 0.1 and 1 mg/kg prevented the development of significant brain acidosis throughout the four ischemic insults. L-NAME at 10 mg/kg reduced preischemic rCBF by 21% (P < 0.05) and did not mitigate brain acidosis after the third and fourth ischemic insults. Brain intracellular pH returned toward baseline after the 3-h final reperfusion in all groups. NADH redox state was significantly (P < 0.05) elevated from baseline controls in all groups during the last three ischemic insults. During the final reperfusion period, NADH redox state returned toward baseline values only in the 0.1 mg/kg L-NAME and ischemic control group. In conclusion, low-dose L-NAME attenuated brain acidosis independent from rCBF changes during intermittent, moderate focal cerebral ischemia.

The purpose of this study was to test the hypothesis that the efficacy of 7-nitroindazole (7-NI), a selective neuronal nitric oxide (NO) synthase (NOS) inhibitor, is pH dependent in vivo during focal cerebral ischemia. Wistar rats underwent 2 h of focal cerebral ischemia under 1% halothane anesthesia. 7-NI, 10 and 100 mg/kg in 0.1 ml/kg DMSO, was administered 30 min before occlusion. Ischemic brain acidosis was manipulated by altering serum glucose concentrations. Confirmation of the effects of these serum glucose manipulations on brain intracellular pH (pHi) was confirmed in a group of acute experiments utilizing umbelliferone fluorescence. The animals were euthanized at 72 h for histology. 7-NI significantly ( P < 0.05) reduced infarction volume in both the normoglycemic by 93.3% and hyperglycemic animals by 27.5%. In the moderate hypoglycemic animals, the reduction in infarction volume did not reach significance because moderate hypoglycemia in itself dramatically reduced infarction volume. We hypothesize that a mechanism to explain the published discrepancies on the effects of neuronal NOS inhibitors in vivo may be due to the effects by differences in ischemic brain acidosis on the production of NO.

An infrared microscope was used for the remote detection of the surface temperature of the cerebral cortex of experimental cats. With this instrument a qualitative assessment of the circulation of the cerebral cortex can be made without interference with the integrity of the brain or vascular tissues or the reactivity of blood vessels. Although the instrument is sensitive enough to detect minor changes of cortical blood flow, its use appears limited to the detection of rapid or transient changes of cerebral circulation and is not suitable for long-term measurements of surface temperature of the brain.

Regional cerebral blood flow (rCBF) measurements with krypton-85 (100 separate determinations) were compared in squirrel monkeys anesthetized with sodium pentobarbital (a cerebral vasoconstrictor) and halothane (a cerebral vasodilator) before, during, and after middle cerebral artery (MCA) occlusion. Prior to MCA occlusion, a normal physiological response to alterations in arterial carbon dioxide tensions (Paco 2 ) was demonstrated in both groups of monkeys; the cerebral vascular resistance was significantly lower in those anesthetized with halothane. During ischemia, there was loss of autoregulation and a failure to respond to alterations in Paco 2 , in both groups. Flow in the ischemic region remained uniform in the barbiturate group but decreased progressively in the halothane group, suggesting a "paradoxical response" to the dilating agent. Reactive hyperemia (luxury perfusion) was demonstrated in both groups after restoration of flow. The use of a beta-emitting isotope ensured that measurements in regions of ischemia accurately reflected rCBF and were free of the artifacts ("look through" and Compton scatter) related to use of a gamma-emitting indicator.

The fluorescence of reduced nicotinamide adenine dinucleotide (NADH) from cerebral cortex was measured before, during, and after middle cerebral artery (MCA) occlusion and then at death of the animal. In normal cortex, NADH remained constant throughout a wide range of variations in blood pressure and Pa co co2 . In ischemic cortex, NADH levels were higher in hypovolemic hypotensive animals than in normotensive normovolemic animals. Neither hypercapnia nor hypocapnia was effective in decreasing NADH in regions of ischemia, but the latter was associated with a degree of hypotension that interfered with interpretation of data. NADH returned to normal with restoration of flow, supporting the reversibility of this degree of ischemia. The high levels of NADH at death, compared to those during ischemia, are consistent with incomplete ischemia in this model of cerebral infarction.

Reduced nicotinamide adenine dinucleotide (NADH) fluorescence was recorded from an avascular area on the squirrel monkey cortex prior to, during, and after focal incomplete ischemia. By using the instrumentation described, stable recordings were obtained free from hemoglobin artifact and with only minimal photodecomposition. Pentobarbital was compared to urethane and halothane as the anesthetic agent and was found acceptable for these types of studies in the dosages used. NADH levels were constant prior to ischemia, increased during ischemia, returned to pre-ischemic levels after restoration of blood flow, and then increased greatly at death produced by anoxia. The use of the infrared microscope for semiquantitative measurements of cortical blood flow throughout the duration of these acute studies was investigated and found to be reliable.

Regional cerebral blood flow (CBF) was measured (intra-arterial injections of 133 Xe) and electroencephalograms (EEG) were recorded periodically before, for two hours during, and for one and one-fourth hours after middle cerebral artery (MCA) occlusion in 20 squirrel monkeys ( Saimiri sciureus ). A CBF-Pa co co2 response curve for these animals under barbiturate anesthesia was created from CBF values prior to MCA occlusion and during the time a steady state was being achieved. The animals were subdivided into four groups (five monkeys in each) on the basis of Pa co co2 values: 20, 36, 40, and 60 mm Hg. CBF values from this study were compared to previous results obtained with 35 Kr. The phenomenon of "look through" and the importance of recognizing this artifact and its significance in analyzing CBF results in areas of focal ischemia are discussed. The present results were correlated with cerebral ATP and lactate concentrations in ischemic regions determined in previous studies using this preparation at these Pa co co2 values and at comparable time intervals before, during, and after MCA occlusion. The EEG appears to reflect the state of ischemic brain accurately. However, CBF measured by the 133 Xe method can be misleading in regard to the true degree of ischemia resulting from occlusion of an intracranial vessel and cannot be relied on to demonstrate accurately "steal" or "reverse steal" due to changes in Pa co co2 .

Background and Purpose —During focal cerebral ischemia, the ischemic penumbra or border-zone regions of moderate cortical blood flow reductions have a heterogeneous development of intracellular cortical acidosis. This experiment tested the hypotheses that (1) this acidosis is secondary to glucose utilization and (2) this intracellular acidosis leads to recruitment of potentially salvageable tissue into infarction. Methods —Brain pH i , regional cortical blood flow, and NADH redox state were measured by in vivo fluorescent imaging, and infarct volume was assessed by triphenyltetrazolium chloride histology. Thirty fasted rabbits divided into 6 groups of 5 each were subjected to 4 hours of permanent focal ischemia in the presence of hypoglycemia (≈2.8 mmol/L), moderate hyperglycemia (≈11 mmol/L), and severe hyperglycemia (>28 mmol/L) under either normoxia or moderate hypoxia (Pa o 2 ≈50 mm Hg). Results —Preischemic hyperglycemia led to a more pronounced intracellular acidosis and retardation of NADH regeneration than in the hypoglycemia groups under both normoxia and moderate hypoxia in the ischemic penumbra. For example, 4 hours after ischemia, brain pH i in the severe hyperglycemia/normoxia group measured 6.46, compared with 6.84 in the hypoglycemia/normoxia group ( P <0.01), and NADH fluorescence measured 173% compared with 114%. Infarct volume in the severe hyperglycemia/normoxia group measured 35.1±6.9% of total hemispheric volume, compared with 13.5±4.2% in the hypoglycemia/normoxia group ( P <0.01). Conclusions —Hyperglycemia significantly worsened both cortical intracellular brain acidosis and mitochondrial function in the ischemic penumbra. This supports the hypothesis that the evolution of acidosis in the ischemic penumbra is related to glucose utilization. Furthermore, the observation that hypoglycemia significantly decreased infarct size supports the postulate that cortical acidosis leads to recruitment of ischemic penumbra into infarction.