Afferent reinnervation of the autotransplanted heart in dogs.

Patients have been observed with a chest pain syndrome after cardiac transplantation. For this pain to be cardiac in origin the afferent nerves carrying sensory information from the heart would have to reinnervate the heart. A previous study in dogs indicated that afferent reinnervation is uncommon during the first 2 years after transplantation. The purpose of this study was to determine whether afferent reinnervation of the heart occurs in the long term. The decreases in arterial pressure and renal nerve activity resulting from chemical stimulation of left ventricular sensory receptors with vagal afferents with cryptenamine (veratrum alkaloid) were assessed in three dogs 8 to 12 years and in four dogs 6 to 8 weeks after cardiac autotransplantation and in six sham-operated dogs (thoracotomy-pericardiotomy 6 to 8 weeks before study). Responses of renal nerve activity to physiologic stimulation of cardiac receptors by volume expansion were also determined. Left ventricular cryptenamine inhibited renal nerve activity by 72 +/- 8% in dogs with long-term and by 10 +/- 6% in dogs with short-term autotransplantation and by 92 +/- 5% in sham-operated dogs. Decreases in mean arterial pressure in these groups were 34 +/- 4, 11 +/- 3 and 67 +/- 16 mm Hg, respectively. Volume expansion inhibited renal nerve activity in long-term autotransplant (43%) and sham-operated (48%) groups but less in the short-term transplant group (33%) for comparable increases in cardiac filling pressure. It is concluded that in dogs there is extensive afferent reinnervation of the long-term autotransplanted heart that results in relatively normal cardiopulmonary baroreflex responses to volume expansion.(ABSTRACT TRUNCATED AT 250 WORDS)

The inhibition of platelet aggregation of metastatic H-ras-transformed 10T1/2 fibroblasts with castanospermine, an N-linked glycoprotein processing inhibitor.

A series of T24-H-ras-transformed 10T1/2 fibroblasts with varying metastatic potential was tested for the ability to aggregate platelets. Results indicate that although platelet activation was always detected in the highly metastatic cells, some non-metastatic cells also have the ability to cause platelet aggregation, suggesting that this is a necessary but not sufficient characteristic of the metastatic phenotype. Apyrase, an ADP scavenger, effectively inhibited platelet aggregation by metastatic cells, however, there was no significant increase in ADP secretion or relation to the ability of the tumor cells to activate platelets. Hirudin, a thrombin inhibitor, did not affect aggregation, suggesting that the pathway of activation is thrombin-independent. The glycoprotein processing inhibitor, castanospermine, which reduces glycosidase I activity and metastatic capability, inhibited the ability of metastatic cells to cause platelet aggregation. However, another inhibitor of oligosaccharide processing, swainsonine, which inhibits mannosidase II activity and does not reduce metastasis, had no effect on platelet aggregation. These results show that the integrity of N-linked oligosaccharide structure of glycoproteins is an important feature of the ability of ras-transformed fibroblasts to activate platelets.

Peripheral visual field testing in glaucoma by automated kinetic perimetry with the Humphrey Field Analyzer.

A Humphrey automated perimeter was used to measure the central 24 degrees of vision with static threshold targets and the peripheral field with two automatic kinetic stimuli in 100 eyes of 100 patients with glaucoma or a suspicion of glaucoma and to compare the additional information gained with the peripheral tests. The peripheral visual field supported the diagnosis made with central field testing in approximately one third of the eyes and added additional diagnostic information in another fourth of the cases. In 4% of patients a normal central field was associated with a glaucomatous peripheral defect. Virtually all peripheral defects were in the nasal quadrant, and the more sensitive isopter uncovered the vast majority of the defects.

Occlusive summation of carotid and aortic baroreflexes in control of renal nerve activity.

We recently reported that denervation of aortic or carotid baroreceptors impaired baroreflex control of heart rate but not of hindlimb vascular resistance or lumbar sympathetic nerve activity. Since baroreflex control of sympathetic outflow to different vascular beds is nonuniform, we determined whether carotid or aortic baroreceptor denervation would impair baroreflex control of renal nerve activity. Experiments were performed in 23 alpha-chloralose-anesthetized rabbits. Phenylephrine and nitroglycerin were infused to raise or lower arterial pressure. Pressure elevation inhibited and pressure reduction increased renal nerve activity. The linear regression relationships between changes in arterial pressure and percent change in renal nerve activity were determined with baroreflexes intact and after aortic or carotid denervation. Neither carotid nor aortic denervation alone impaired baroreflex control of renal nerve activity. In nine experiments responses were determined first with vagi sectioned. The results were comparable to those obtained without prior vagotomy. Our data indicate that one group of baroreceptors (aortic or carotid) exerts full control of renal nerve activity and that aortic and carotid baroreflex influences on renal nerve activity add by occlusive or mutual inhibitory summation.

Central abnormality in baroreflex control of renal nerves in hypertension.

The purpose of our study was to determine if there is a central abnormality in the arterial baroreceptor reflex control of renal nerve activity in renal hypertension. We recorded simultaneously the changes in aortic (input) and renal (output) nerve traffic during phenylephrine-induced increases in arterial pressure in 14 normotensive and 11 hypertensive rabbits [mean arterial pressure (+/- SE) in conscious state 106 +/- 2 and 141 +/- 6 mmHg, respectively]. Changes in aortic nerve traffic were considered representative of changes in total arterial baroreceptor input to the central nervous system. Renal nerve traffic was inhibited by 5.2 +/- 0.5% per mmHg rise in arterial pressure in normotensive rabbits but by only 2.5 +/- 0.3% per mmHg in hypertensive rabbits (P less than 0.05). Increases of aortic nerve traffic during increases in arterial pressure were similar in the two groups. These data suggest that there is a central abnormality in the baroreflex control of renal nerve activity in renal hypertensive rabbits. This hypothesis was tested further by sectioning vagal, carotid, and aortic nerves and stimulating electrically the left aortic depressor nerve while recording changes in blood pressure and renal sympathetic nerve traffic. Decreases of renal traffic during stimulation of myelinated fibers alone were strikingly impaired (P less than 0.001) at all frequencies in hypertensive rabbits. Responses were not impaired significantly during stimulation of myelinated plus nonmyelinated fibers. Arterial pressure decreases were not different during stimulation of myelinated fibers or of both myelinated and nonmyelinated fibers.(ABSTRACT TRUNCATED AT 250 WORDS)

Superoxide anion radical does not mediate vasodilation of cerebral arterioles by vasoactive intestinal polypeptide.

We examined the hypothesis that oxygen radicals may mediate the vasodilator effect of VIP on cerebral arterioles in cats equipped with cranial windows. The appearance of superoxide anion radical in cerebral extracellular space during VIP application was examined by measuring the rate of superoxide dismutase (SOD)-inhibitable reduction of nitroblue tetrazolium (NBT). Although VIP (1 and 10 micrograms/ml) caused substantial reduction of NBT, the rate of the SOD-inhibitable portion was not significantly different from zero. We also examined the effect of scavenging of superoxide and hydrogen peroxide by topical application of SOD plus catalase on the vasodilator effect of VIP (0.05-1.0 microgram/ml). The dilation in response to VIP was not significantly affected in either large or small arterioles by scavenging of superoxide and hydrogen peroxide. We conclude that VIP does not cause generation of superoxide and that superoxide or other reactive oxygen species derived from it, such as hydrogen peroxide and hydroxyl radical, are not mediators of the cerebral vasodilation caused by VIP.

Physical and sexual abuse issues among youths with substance use problems.

OBJECTIVES: To evaluate the prevalence of reported physical and sexual abuse among youths with substance use problems, to explore whether youths report relying on substances to cope with the abuse, and to examine whether individual factors related to substance use were associated with the outcome measures of reported physical abuse, sexual abuse, and using substances to cope. METHOD: We assessed 287 male and female youths (age 14 to 24 years) who presented for help for substance use problems, using a semistructured interview that focused on substance use, history of previous sexual and physical abuse, and coping strategies. RESULTS: One-half of the female youth substance abusers reported having been sexually abused (50.0%), while male youth substance users reported a significantly lower rate (10.4%). Similarly, one-half of the female youths had a history of physical abuse (50.5%), and males again had a lower rate (26.0%). Of those who endorsed a history of abuse, more females (64.7%) than males (37.9%) reported using substances to cope with the trauma. Specific associations between the outcome measures and substance use variables were found for youths in both sexes. CONCLUSION: These findings underscore the importance of why clinicians should explore abuse issues with substance-using youth of both sexes. Identifying concurrent factors will help provide better intervention strategies. Suggestions for assessing sexual and physical abuse in youths with substance use disorders are provided.