Acute Transient Changes Research Articles

Mathematically arterialised venous blood is a stable representation of patient acid-base status at steady state following acute transient changes in ventilation.

Hyper- or hypoventilation are commonly occurring stress responses to arterial puncture around the time of blood sampling and have been shown to rapidly alter arterial blood acid–base parameters. This study aimed to evaluate a physiology-based mathematical method to transform peripheral venous blood acid–base values into mathematically arterialised equivalents following acute, transient changes in ventilation. Data from thirty patients scheduled for elective surgery were analysed using the physiology-based method. These data described ventilator changes simulating ‘hyper-’ or ‘hypoventilation’ at arterial puncture and included acid–base status from simultaneously drawn blood samples from arterial and peripheral venous catheters at baseline and following ventilatory change. Venous blood was used to calculate mathematically arterialised equivalents using the physiology-based method; baseline values were analysed using Bland–Altman plots. When compared to baseline, measured arterial and calculated arterialised values at each time point within limits of pH: ± 0.03 and PCO2: ± 0.5 kPa, were considered ‘not different from baseline’. Percentage of values considered not different from baseline were calculated at each sampling timepoint following hyper- and hypoventilation. For the physiological method, bias and limits of agreement for pH and PCO2 were -0.001 (-0.022 to 0.020) and -0.02 (-0.37 to 0.33) kPa at baseline, respectively. 60 s following a change in ventilation, 100% of the mathematically arterialised values of pH and PCO2 were not different from baseline, compared to less than 40% of the measured arterial values at the same timepoint. In clinical situations where transient breath-holding or hyperventilation may compromise the accuracy of arterial blood samples, arterialised venous blood is a stable representative of steady state arterial blood.

The Effect of Therapy on Tumour Vascular Function

It has been established that malignant tissue as a consequence of abnormal morphogenesis has a structurally abnormal blood supply. These structural and as a consequence functional differences between normal and neoplastic vasculature provide a basis for selective modulation of tumour vascular function. Agents have been identified which can induce both irreversible and reversible effects on tumour blood flow. Hyperthermia, photodynamic therapy, tumour necrosis factor and flavone acetic acid are known to elicit most of their anti-tumour effect via irreversible changes in tumour vascular function. In addition to the extensive tumour cell kill and thus therapeutic potential provided by such chronic modulation of blood flow, acute transient changes in macroregional and microregional tumour blood flow could also play an important role if used appropriately with conventional therapies. The use of this latter type of modulation is discussed with reference to known examples of such 'vasoactive' compounds. It is also emphasized that blood flow changes induced in tumour tissue can be a 'double-edged sword' with detrimental consequences for therapeutic outcome if inappropriate changes are induced, for example, reductions in flow at the time of conventional radiotherapy or chemotherapy by agents not considered to be 'vasoactive'. To emphasize this point examples of blood flow modulation by pimonidazole and cis-platinum, agents that are used in conjunction with radiotherapy, are described.

1673 IN VIVO VARIATION OF BRAIN OXIDATIVE metabolism with therapeutic lumbar PUNCTURE (LP)

Sequential cerebral spectra of phosphorus-containing compounds, ATP, phosphocreatine (Pcr), inorganic phosphate (Pi), phosphodiester (PD), and phosphomonoester (PME), by 31-P nuclear magnetic resonance (NMR) were obtained in a severely asphyxiated premature infant with hydrocephalus and seizures. Between days 2-20, 10 therapeutic LP's were done and NMR cerebral spectra were obtained pre (a) and post (p) LP. Pcr/Pi (normal x = 1.01), a measure of bioenergetic reserve, was low at 48h; Left (L) = 0.50, Right (R) = 0.60. After the initial LP, Pcr/Pi rose to L=1.4 and R=0.6. After subsequent LP's, a sharp decrease in Pcr/Pi was followed by a rebound (a LP, L=1.50, R=1.03; p LP, L=0.87, R=0.62; 1½ hrs p LP, L=1.52, R=1.66). Pcr/Pi increased by day 8 (L=1.52, R=1.60) then stabilized during the next month (L=1.0, R=0.8). Tissue pH did not change significantly (day 5: a LP=7.07, p LP=7.02, 1½ hrs p LP=7.08; day 8: a LP=7.12, p LP=7.02, 1½ hrs p LP=1.12). PME/β-ATP, a precursor in membrane biosynthesis, declined (day 2, L=3.15, R=2.53; day 46, L=1.46, R=1.17) but changed inconsistently post LP. Acute changes in Pcr/Pi and PME/β-ATP represent changes in local cerebral metabolism. Removal of 5 cc of CSF may result in acute intracerebral tissue shifts, acute hydrostatic changes with probable effects on CSF and cerebral blood flow, and hence provision of metabolic substrate to brain tissue. These data suggest that acute transient changes in Pcr/Pi and PME/β-ATP, representing changes in local cerebral metabolism, reflect general changes in cerebral metabolic or seizure activity.

Opioid and neurotransmitter regulation of pituitary gonadotropin-releasing hormone (GnRH) receptors in the ovariectomized estradiol-treated rat: role of altered GnRH secretion.

An acute transient fall in the number of pituitary GnRH receptors (GnRH-R) is observed before the preovulatory gonadotropin surge in cycling rats and before the afternoon daily gonadotropin surge in ovariectomized estradiol-treated rats. In the latter model, this fall can be reproduced by administration of the opioid antagonist naloxone, whereas the opioid agonist morphine acutely increases GnRH-R. In this study we investigated the mechanisms of this opioid effect and examined the effects of other neurotransmitter substances on modulation of pituitary GnRH-R. Administration of the dopaminergic agonists bromocriptine and L-dopa or the alpha-adrenergic receptor blocker phenoxybenzamine elevated GnRH-R acutely from average basal values of 240 +/- 22 and 254 +/- 21 fmol/mg protein to maximal values of 374 +/- 49, 441 +/- 67 and 461 +/- 75 fmol/mg, respectively, whereas the alpha-adrenergic agonist clonidine transiently decreased GnRH-R to 186 +/- 19 fmol/mg. Placement of radiofrequency lesions in the mediobasal hypothalamus or pretreatment with anti-GnRH serum completely abolished the ability of both morphine and naloxone to modulate the number of GnRH-R. These data indicate that the opioid-induced modulation of pituitary GnRH-R requires an intact hypothalamus and that both dopaminergic and alpha-adrenergic neurotransmitter systems may be involved. The final step of this action probably involves acute modulation of GnRH secretion (altered frequency and/or amplitude), which results in acute transient changes in the number of pituitary GnRH-R.

Effects of continuous administration of angiotensin II on ventricular performance

The effects of angiotensin II on circulatory dynamics and coronary blood flow were studied in the cat. With equal single doses of angiotensin II and norepinephrine a greater blood pressure response occurred with angiotensin. With continuous administration of angiotensin II a large initial blood pressure response occurred, but rapidly returned to an intermediate value. During this time the animal was refractory to further single doses. A sustained large increase of ventricular contractility was readily demonstrated with the continuous administration of norepinephrine, but could not be demonstrated with equal amounts of angiotensin II. Acute transient changes of ventricular contractility were observed. Frequently an acute increase of both stroke work at a given filling pressure, and mean rate of ejection occurred. Occasionally, however, marked acute myocardial depression, which rapidly returned to control values, was observed. In about one-third of the preparations prolonged myocardial depression was observed following a period of continuous angiotensin II infusion. This was in sharp contrast to continuous norepinephrine infusion following which myocardial depression was never observed. Measurements of coronary blood flow indicated that when ventricular work was maintained constant, continuous angiotensin II infusion was frequently associated with a transient reduction of coronary flow. This was usually small, but occasionally marked. During this phase concomitant myocardial depression was evident. Continuous norepinephrine infusion produced only an increase of coronary blood flow with an associated increase of myocardial contractility.