Effects of decreasing arterial blood pressure on cerebral blood flow in the baboon. Influence of the sympathetic nervous system.

The influence of the sympathetic nervous system on the cerebral circulatory response to graded reductions in mean arterial blood pressure was studied in anesthetized baboons. Cerebral blood flow was measured by the 133Xe clearance method, and arterial blood pressure was decreased by controlled hemorrhage. In normal baboons, the constancy of cerebral blood flow was maintained until mean arterial blood pressure was approximately 65% of the base-line value; thereafter, cerebral blood flow decreased when arterial blood pressure was reduced. Superior cervical sympathectomy of 2-3 weeks duration did not affect the normal response. In contrast, both acute surgical sympathectomy (cervical trunk division) and alpha-receptor blockade (1.5 mg/kg of phenoxybenzamine) enhanced the maintenance of cerebral blood flow in the face of hemorrhagic hypotension in that cerebral blood flow did not decrease until mean arterial blood pressure was approximately 35% of the base-line value. The results indicate that the sympathetic nervous system is not involved in the maintenance of cerebral blood flow in the face of a fall in arterial blood pressure. Indeed, the implication is that the sympathicoadrenal discharge accompanying hemorrhagic hypotension is detrimental to, rather than responsible for, cerebral autoregulation.     

The cardiovascular effects of cyclopropane in the intact, decerebrate and pithed rabbit preparations.

1 The anaesthetic cyclopropane was given to intact, decerebrate and pithed unanaesthetized rabbit preparations to determine the relative importance in vivo of its central and peripheral cardiovascular effects. 2 Cyclopropane elevated both the heart rate and the mean arterial pressure in the intact rabbit. 3 In the decerebrate rabbit, cyclopropane elevated the heart rate and efferent cervical preganglionic nerve activity and diminished the magnitude of these components of the aortic baroreceptor reflex, the mean arterial pressure being unaffected. 4 Apart from slight myocardial depression, cyclopropane was largely without effect in the pithed rabbit. 5 It is concluded that cyclopropane produces its cardiovascular effects by supra-collicular activation eliciting an elevation of mean arterial pressure, a central sub-collicular activation producing an increase in heart rate, and that in vivo the peripheral effects of cyclopropane are of minimal importance in comparison to these central effects.     

Succinate links TCA cycle dysfunction to oncogenesis by inhibiting HIF-alpha prolyl hydroxylase

Several mitochondrial proteins are tumor suppressors. These include succinate dehydrogenase (SDH) and fumarate hydratase, both enzymes of the tricarboxylic acid (TCA) cycle. However, to date, the mechanisms by which defects in the TCA cycle contribute to tumor formation have not been elucidated. Here we describe a mitochondrion-to-cytosol signaling pathway that links mitochondrial dysfunction to oncogenic events: succinate, which accumulates as a result of SDH inhibition, inhibits HIF-alpha prolyl hydroxylases in the cytosol, leading to stabilization and activation of HIF-1alpha. These results suggest a mechanistic link between SDH mutations and HIF-1alpha induction, providing an explanation for the highly vascular tumors that develop in the absence of VHL mutations.     

Spigelian Hernia

We report on the evolution in concept and techniques that allowed us to improve the treatment of spigelian hernia, operable in day surgery in 90% of cases and through a preperitoneal and recently a preperitoneal and subfascial prosthetic repair (PHS). Background data. We propose an innovative use of the PHS mesh for spigelian hernia repair. With this new implementation, we confront the standard surgical technique and its postoperative period. Methods. From January 1992 to March 2004, we performed 2,500 hernia surgical operations, including 32 spigelian hernia repairs (1.3% of total case series). The first surgical approach used for 20 of these 32 patients (62.5% of total spigelian hernias), all electively operated on, was a classical preperitoneal repair (Wantz), performed when possible by size of defect and weight (Body Mass Index) of the patient, under local anesthesia and on a day-surgery basis. Our new modified technique takes place through the insertion of a PHS large-type mesh, whose bottom underlay portion lies flat in the preperitoneal space with the connector obliterating the hernial orifice and with the overlay portion lying on the internal oblique muscle, covered by the aponeurosis of the external oblique muscle. Results. Our modification to the classical technique consisted only in the application of a product, such as the PHS, in a hernia defect, which presented with an orifice of the size of the connector and, therefore, was easily repairable with the use of the PHS device. This approach is easier than the preperitoneal approach, its always suitable for local anaesthesia, and it gives a more comfortable postoperative period. The surgical approach may be performed completely in day surgery. Conclusions. We believe that spigelian hernia surgical repair should always be performed by means of a preperitoneal prosthesis under local anaesthesia when the patients clinical and physical conditions allow for it, always in day surgery, and using the PHS mesh when the hernia defect size fits with the connector diameter. This last possibility seems to be easier and more comfortable for the patient in the postoperative period.