An in vivo study of the effects of ischaemia on uterine contraction, intracellular pH and metabolites in the rat.

Abstract

1. There are no data concerning the functional or metabolic effects of hypoxia in vivo in smooth muscle. We have therefore used 3"P-NMR spectroscopy and intra-uterine pressure measurements to examine simultaneously, in vivo, the effect of ischaemia on uterine metabolites, intracellular pH (pHi) and force.2. A 1-2 cm portion of uterus from day 1 postpartum anaesthetized rats was exteriorized and an NMR surface coil placed on it. A balloon catheter in the uterine lumen recorded intra-uterine pressure changes from the same area. Reversible occluders were placed around the uterine artery. 3. Occlusion produced a decrease and then abolition of contractions, within 10 min. In four of five animals contraction was abolished within 2 min. Upon reperfusion force was rapidly restored (1 min), in all preparations. The mean level of force was significantly above control (pre-occlusion) 20-30 min after reperfusion. 4. The NMR data showed a significant fall in [ATP] (28 %) and [phosphocreatine] (34 %) during occlusion. Inorganic phosphate doubled in concentration during this period. Metabolites recovered slowly upon reperfusion, taking 20-30 min to return to preocclusion levels.5. The mean pHi fell from 7-32 to 7 00 upon occlusion and was rapidly reversed upon reperfusion. The changes in pHi closely correlated with the changes in uterine force. Decreases of pHi of a similar magnitude in vitro have previously been shown to abolish contractions; thus it is suggested that during ischaemia in vivo the depression of contraction is caused by the large fall in pHi.The effect of hypoxia or ischaemia in vivo on smooth muscle function, metabolites and intracellular pH (pH1) is unknown. Given the important roles played by smooth muscle cells within the body and the fact that tissue blood flow and oxygenation may well alter under different physiological conditions, it is important that such information be obtained. We have therefore investigated the effects of ischaemia on uterine smooth muscle in vivo.

Hypoxia-induced force increase (HIFI) is a novel mechanism underlying the strengthening of labor contractions, produced by hypoxic stresses

“…An increase of force (intrauterine pressure) of 130-140% on reperfusion was reported and lasted for over 30 min. The significance of these data were not appreciated at the time (4,12). Our protocols (and in vivo studies) were developed to clearly demonstrate the effects of repetitive hypoxia and investigate its mechanism.…”

“…This is known as hypoxic or ischemic preconditioning, and has been best investigated in cardiac muscle (10) and brain (11), where it is considered to be a powerful mechanism for limiting ischemic damage. Given that physiological decreases in oxygenation are part of the normal process of labor (4,12), this finding therefore raised some important questions: What is the effect of brief but repetitive periods of hypoxia on uterine contractility? And, do cycles of brief hypoxia initiate and maintain the progressive augmentation of contractility needed for labor?…”

Effect of metabolic inhibition on intracellular Ca2+, phosphorylation of myosin regulatory light chain and force in rat smooth muscle.

“…The finding that MLC20 phosphorylation levels in tissues depolarized in the absence or presence of agonists were unaffected by cyanide treatment indicates that [ATP] surrounding the myofilaments remained sufficient to support contractile activity (see below) since, under physiological conditions, MLC20 dephosphorylation precedes relaxation (Khromov, Somlyo, Trentham, Zimmermann & Somlyo, 1995 (Wray, 1990). Similarly, in vivo occlusion of the uterine artery of anaesthetized rats resulted in abolition of contractile activity accompanied by only moderate decreases in [ATP] and [phosphocreatine] (Harrison et al 1994). This is in agreement with Hardin, Wiseman & Kushmeric (1992) who suggested that isometric force generation of hypoxic vascular smooth muscle was not limited by the [ATP].…”

Search for T-violation in neutrino oscillation with the use of muon polarization at a neutrino factory

“…By the CPT theorem, in vacuum, observation of T-violation is identical to observation of CP-violation. Even in a terrestrial oscillation experiment, since a possible T-odd effect from asymmetric matter density profile in the earth is very small [12], this T-reversed difference reveals as a very clean signal [2,13] on the imaginary phase in the lepton sector [2,9,10,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26].…”