Effects of thiopental on resistance vessels in cat skeletal muscle

Barbiturates are used clinically as anaesthetics and to reduce raised intracranial pressure. One side effect is hypotension, usually ascribed to a depression of cardiac contractility, while their effects on the resistance vessels are more controversial: both vasodilation and vasoconstriction have been described. This study analyzes the effects of thiopental on basal vascular tone in the cat skeletal muscle. We found that total resistance increased by almost 20% at low (50 mumol/l) and decreased down to about 50% of control at high (350 mumol/l) plasma concentrations of thiopental. The vasoconstriction dominated in the large arterioles (i.d. greater than 25 microns) and the vasodilation in the small arterioles (i.d. less than 25 microns). A dose-dependent inhibition of myogenic vascular reactivity (here defined as the maximum resistance increase to a transient rise in transmural pressure) coincided with the vasodilation. Autoregulation of blood flow was depressed by thiopental. During vasoconstriction there was a net transcapillary fluid absorption and during vasodilation a net fluid filtration. The fluid movements could be ascribed to variations in capillary hydrostatic pressure. If applicable to the cerebral circulation these results suggest that thiopental at high plasma concentrations might induce, instead of reduce, interstitial brain oedema

Effects of calcium antagonists on myogenic and neurogenic control of resistance and capacitance vessels in cat skeletal muscle

The effects of five different calcium antagonists (diltiazem, felodipine, nifedipine, nimodipine, and verapamil) on cat skeletal muscle resistance and capacitance vessels were studied in a whole organ preparation. These calcium antagonists seemed to have the similar qualitative effects on these vascular functions. Calcium antagonists were found to be potent inhibitors of myogenic vascular reactivity (here defined as the maximal increase in flow resistance evoked by a sudden rise of transmural pressure). Basal vascular tone and vascular tone induced by low frequency stimulation of sympathetic nerves were both less sensitive to these drugs than vascular tone induced by myogenic vascular reactivity. Sympathetically mediated vascular tone at high stimulation frequencies seemed to be least sensitive. Further, resistance vessels were much more sensitive to these drugs than capacitance vessels. Finally, basal tone in the large bore arterioles were more sensitive than in the small bore arterioles, a surprising finding which was interpreted with the aid of computer simulations using a mathematical model of local vascular control in cat skeletal muscle. The model suggested that this difference could be due to a delicate interaction between myogenic vascular reactivity and metabolic vascular control. It is suggested that the inhibition of myogenic vascular reactivity is a factor contributing to the edema formation of calcium antagonists

Treatment of intracranial hypertension and aspects on lumbar dural puncture in severe bacterial meningitis - Reply

BACKGROUND: Brain stem herniation due to raised intracranial pressure (ICP) is a common cause of mortality in severe bacterial meningitis, but continuous measurements of ICP and the effects of ICP-reducing therapy in these patients have, to our knowledge, not been described. METHODS: During a four-year period, an ICP-monitoring device was implanted in patients admitted to our hospital with severe bacterial meningitis and suspected intracranial hypertension. ICP above 20 mmHg was treated using the Lund Concept, which includes antihypertensive therapy (beta1-antagonist,alpha2-agonist), normalization of the plasma colloid osmotic pressure and the blood volume, and antistress therapy. RESULTS: ICP above 20 mmHg was found in all 12 patients studied. It was effectively reduced in all but two patients, who died. Both patients had a low cerebral perfusion pressure (<10 mmHg), dilated pupils at start of therapy and were beyond recovery. Radiological signs of brain swelling were present in only five patients. Seven patients recovered fully, while mild audiological impairment was observed in two and minor neurological sequelae in one patient. Eight patients showed signs suggesting imminent brain stem herniation before start of ICP-reducing treatment, seven of whom had been subjected to diagnostic lumbar dural puncture shortly before development of the brain stem symptoms. These symptoms gradually regressed after initiation of therapy, and in one patient reversal of brain stem herniation was documented by MRI. CONCLUSIONS: Severe bacterial meningitis can be associated with increased ICP, which can be reduced using the Lund Concept. The high survival rate, the low frequency of sequelae and the reversal of signs of imminent brain stem herniation in these high-risk patients indicated beneficial effects of the intervention. The study confirms earlier observations that lumbar dural puncture is potentially hazardous in patients with intracranial hypertension, because it may trigger brain stem herniation. A normal CT brain scan does not rule out intracranial hypertension