The chronic vascular and haemodynamic response after permanent bilateral common carotid occlusion in newborn and adult rats.

Vascular growth and redistribution of flow can compensate for arterial occlusion and possibly reduce the effects of hypoperfusion. As yet there is limited information on the age-dependent nature of vasculature remodelling. In this study, we have monitored the vascular and morphologic changes using magnetic resonance imaging and histology in a chronic bilateral common carotid artery occlusion (BCCAO) model in both newborn and adult rats. Acutely, cerebral blood flow (CBF) decreased immediately after BCCAO, producing a state of oligemic hypoperfusion. At 6 months after BCCAO in both adult and neonatal rats, the CBF had normalised at control values. To investigate the underlying mechanism for the return of CBF to control values, intra- and extracerebral magnetic resonance angiograms (MRAs) were acquired. As expected, signal from the common carotid arteries was present in the sham-operated rats, but was absent in the BCCAO animals. India ink angiograms demonstrated more tortuous basilar arteries in the adult rats post-BCCAO and MRAs demonstrated more extracerebral midline collaterals in the neonatal rats post-BCCAO, indicating different modes of vascular adaptation dependent on the age at onset of the insult. Both groups had collateral vessels arising from the vertebral arteries, and BCCAO was also associated with increased diameter of basilar, posterior cerebral, posterior communicating, internal carotid, middle cerebral and anterior cerebral arteries. Our study suggests that the developing and mature animals exhibit different patterns of vascular remodelling and that the BCCAO hypoperfusion model will be useful for investigating age-dependent vascular events in response to vaso-occlusive disease.

The effects of moderate hypothermia on energy metabolism and serum inflammatory markers during laparotomy.

The objective of this study was to investigate energy metabolism of the gut and liver as well as serum inflammatory cytokines following exploratory laparotomy at moderate hypothermia. Two groups of rats were studied, (n=6-8/group); laparotomy at normothermia for 120 min and laparotomy at hypothermia (32-33 degrees C) for 120 min. Study 1: Intestinal glucose, succinate, lactate, phosphocreatine, and ATP as well as hepatic glucose, succinate, lactate, and ATP were measured in terms of micromole per gram using magnetic resonance spectroscopy. Study 2: Serum levels of TNF-alpha, IL-1beta, LPS-inducible chemokine (LIX), and sICAM-1 were measured by ELISA. Histology of the gut and liver were interpreted. Data are expressed as mean and SEM. In Study 1, laparotomy at hypothermia caused an increase in intestinal glucose levels (0.78+/-0.03 vs. 1.29+/-0.11, P=0.0012) with a decrease in hepatic lactate levels (0.82+/-0.04 vs. 0.44+/-0.06, P<0.001). There were no differences in the other metabolites between the two groups. In Study 2, there were no differences in serum TNF-alpha, IL-1beta, LIX, or sICAM-1 between the two groups. Histological features of the gut and liver among groups were comparable. In conclusion, the intestine and liver react to hypothermia differently. However, levels of high-energy phosphates in both organs are not affected by hypothermia suggesting adequate energy for the organs. It is unlikely that hypothermia induces either systemic inflammatory response or hypoxic damage to the intestine and liver in this model.

Effects of hypothermia on ischaemic depolarisation in brain : a comparison of responses in rat and gerbil.

The latency of development of ischaemic depolarization (LID) has been used to compare the relative effects of different levels of hypothermia on ischaemic responses in brains of rat and gerbil, using a model with imposed complete cessation of cerebral blood flow (CBF=0). At temperatures reducing from 37 degrees C to 20 degrees C, the LIDs were consistently shorter in the gerbil than in the rat. For example, at 37 degrees C the LID in the gerbil was 0.71+/- 01.2 min, and in the rat, 1.37 +/- 0.02 min respectively (P<0.01), whilst at 20 degrees C, the values were 5.48 +/- 0.25 min and 7.30 +/- 0.76 min (P<0.01). However, the relative effects of hypothermia on each species were similar (by linear regression with slopes of -0.29 and -0.35 min/degree C in the two species). There may be underlying differences in brain biophysics or structure between species, but in spite of this, applied hypothermia still imposes a similar depression on the development of ischaemic damage. Both models may thus be used in studies of brain hypothermia as long as the intrinsic differences are appreciated.

Comparative study of the FAIR technique of perfusion quantification with the hydrogen clearance method.

Arterial spin labeling magnetic resonance methods, including flow-sensitive alternating inversion recovery (FAIR), are becoming increasingly common for the noninvasive quantification of cerebral blood flow (CBF). This report compares the FAIR method with hydrogen clearance. The latter is an established, invasive technique for CBF measurement in animals. Paired readings of CBF were obtained in gerbils to maximize the degree of spatial and temporal correspondence between methods. Flow-sensitive alternating inversion recovery (50 averages, 6.7-minute measurement time) and hydrogen clearance measurements were made concurrently. Cerebral blood flow values measured by both techniques displayed an initial decrease because of the injurious effects of electrode insertion and subsequent recovery. Mixed model regression analysis, structural equations modeling, and a simple concordance correlation coefficient analysis were performed. No evidence of a marked systematic bias in the FAIR measurements was found; mixed model regression analysis yielded relative bias estimates of 0.4 (confidence interval: 3.0, 3.9) mL. 100 g-1. min-1 and -3.7 (-12.1, 4.7) mL. 100 g-1. min-1 at 20 and 100 mL. 100 g-1. min-1, respectively. The principal limitation of the FAIR technique was the magnitude of the random measurement error (imprecision), which had a standard deviation on the order of 10 mL. 100 g-1. min-1.

Intestinal energy metabolism after ischemia-reperfusion: Effects of moderate hypothermia and perfluorocarbons.

PURPOSE: This study investigated the roles of moderate hypothermia and extraluminal oxygenated perfluorcarbon (PFC) on intestinal metabolism after ischemia-reperfusion. METHODS: A model of 30-minute intestinal ischemia followed by 60 minutes of reperfusion was used. The animals were maintained at either normothermia (36.5 to 37.5 degrees C) or moderate hypothermia (31 to 32 degrees C). Four groups of adult rats were studied (n = 8 per group): (A) sham at normothermia, (B) ischemia-reperfusion at normothermia, (C) ischemia-reperfusion at hypothermia and, (D) ischemia-reperfusion with extraluminal oxygenated PFC perfusion during ischemia at normothermia. Intestinal phosphocreatine, ATP and lactate levels were measured. Histologic changes in the intestine were evaluated. RESULTS: Intestinal ischemia-reperfusion at normothermia caused a marked reduction in phosphocreatine and ATP with an increase in lactate. Moderate hypothermia exerted beneficial effects by attenuating the depletion of high-energy phosphates and the elevation of lactate. Extraluminal PFC perfusion during ischemia failed to produce a protective effect on high-energy phosphates, although it reduced lactate accumulation. Moderate hypothermia significantly decreased the degree of mucosal damage. CONCLUSIONS: Whole-body moderate hypothermia protects the small intestine from reperfusion injury as measured both biochemically and histologically. Extraluminal oxygenated PFC administration during ischemia did not protect the intestine from reperfusion injury in this model.