Renal artery stent placement for the management of ischemic nephropathy.

PURPOSE: To evaluate the angiographic and clinical results of percutaneously implanted renal artery endoprostheses (stents) for the treatment of patients with ischemic nephropathy. MATERIALS AND METHODS: During a 52-month period, 45 patients with azotemia (serum creatinine > or = 1.5 mg/dL) and atheromatous renal artery stenosis untreatable by, or recurrent after, balloon angioplasty were treated by percutaneous placement of Palmaz stents. Stent implantation was unilateral in 32 cases and bilateral in 11 cases. Clinical results were determined by measurements of serum creatinine and follow-up angiography. Clinical benefit was defined as stabilization or improvement in serum creatinine level. Angiographic patency was defined as less than 50% diameter recurrent arterial stenosis. RESULTS: Stent placement was technically successful in 51 of 54 (94%) renal arteries. Technical failures were stent misdeployment requiring percutaneous stent retrieval (n = 2) and inadvertent placement distal to the desired position (n = 1). Complications included acute stent thrombosis (n = 1) and early initiation of hemodialysis (within 30 days; n = 1). There were two periprocedural deaths. With use of life-table analysis, clinical benefit was seen in 78% of patients at 6 months (n = 36), 72% at 1 year (n = 24), 62% at 2 years (n = 12), and 54% at 3 years (n = 3). In patients with clinical benefit, average creatinine level was reduced from 2.21 mg/dL +/- 0.91 before treatment to 2.05 mg/dL +/- 1.05 after treatment (P = .018). Lower initial serum creatinine level was associated with a better chance of clinical benefit (P = .05). No other variables affected outcome, including patient age, sex, diabetes, implanted stent diameter, unilateral versus bilateral stent placement, or ostial versus nonostial stent positioning. Conventional catheter angiography or spiral computed tomographic (CT) angiography performed in 19 patients (28 stents) at a mean interval of 12.5 months demonstrated primary patency in 75%. Maintained stent patency appeared to correlate with renal functional benefit. CONCLUSIONS: Percutaneous renal artery stent placement for angioplasty failures or restenoses provides clinical benefit in most patients with ischemic nephropathy.

Renal transplantation in multiple myeloma. Case report and review of the literature.

A patient with end-stage renal disease and known benign monoclonal gammopathy underwent kidney transplantation at Westchester County Medical Center, Valhalla, NY. After surgery, during routine follow-up, the patient had laboratory evidence of frank multiple myeloma. However, she did not show any clinical signs or symptoms of the disease. Four years later, the patient is asymptomatic and continues to have stable renal function. As a result of our experience, and that of others, we support transplantation as a viable option for patients with multiple myeloma.

The effect of an alpha-2 agonist on bladder function and cord histology after spinal cord injury.

Spinal injury in cats is accompanied by urinary bladder and hind limb dysfunction. Ten cats subjected to spinal contusion at the ninth thoracic segment were treated with guanabenz (an alpha-2 agonist) intraperitoneally (0.65 mg./kg.) three hours after injury, and twice daily for eight weeks. An additional six spinal cats were untreated and served as controls. Urodynamic studies were performed on a weekly basis on all animals. Guanabenz modified the vesico-somatic reflex: detrusor-sphincter dyssynergia was either ablated or abolished. In contrast, the controls demonstrated detrusor-sphincter dyssynergia, high residual urine, and spasticity below the lesion. Histological evaluations of the spinal cords revealed that the six paraplegic animals (untreated) suffered marked cavitation of the cord and complete destruction of the grey matter. The five incomplete paraplegic animals (treated) showed minimal cavitation with some preservation of the grey matter. The five ambulators (treated) demonstrated some distortion of grey matter with preservation of white matter. Treatment with guanabenz post traumatic cord injury results in decreased cord cavitation. Detrusor-sphincter dyssynergia is diminished and hind limb function is improved in treated animals.

Ascorbic acid: a putative biochemical marker of irreversible neurologic functional loss following spinal cord injury.

The development of permanent paraplegia in spinal injured cats is accompanied by a large progressive decline in total ascorbic acid (AA) and a transient increase in oxidized (AAox) ascorbate. Since AA is involved in a variety of processes required for normal central nervous system (CNS) performance we suggested that such large ascorbate loss may contribute to derangements in spinal cord function following injury. We now demonstrate that methylprednisolone (15 mg/kg) and naloxone (10 mg/kg), two treatments that preserve neurologic function in this model, rapidly block deteriorating ascorbate status. Naloxone at 1 mg/kg, a treatment providing no therapeutic benefit, has no protective effect on ascorbate. The results strongly support the hypothesis that loss of ascorbate homeostasis reflects irreversible loss of neurologic function following spinal cord injury.

Further studies on free-radical pathology in the major central nervous system disorders: effect of very high doses of methylprednisolone on the functional outcome, morphology, and chemistry of experimental spinal cord impact injury.

The hypothesis that pathologic free-radical reactions are initiated and catalyzed in the major central nervous system (CNS) disorders has been further supported by the current acute spinal cord injury work that has demonstrated the appearance of specific, cholesterol free-radical oxidation products. The significance of these products is suggested by the fact that: (i) they increase with time after injury; (ii) their production is curtailed with a steroidal antioxidant; (iii) high antioxidant doses of the steroidal antioxidant which curtail the development of free-radical product prevent tissue degeneration and permit functional restoration. The role of pathologic free-radical reactions is also inferred from the loss of ascorbic acid, a principal CNS antioxidant, and of extractable cholesterol. These losses are also prevented by the steroidal antioxidant. This model system is among others in the CNS which offer distinctive opportunities to study, in vivo, the onset and progression of membrane damaging free-radical reactions within well-defined parameters of time, extent of tissue injury, correlation with changes in membrane enzymes, and correlation with readily measurable in vivo functions.

Experimental spinal cord injury: treatment with naloxone.

We studied the effect of the opiate antagonist naloxone on the recovery of cats injured with a 400-g-cm impact injury to T-9. The animals were evaluated by recording somatosensory evoked potentials and performing weekly neurological examinations. Several dose schedules were followed. Six of eight cats that received an intravenous or intraperitoneal bolus of naloxone (10 mg/kg) 45 minutes after injury regained the ability to walk. Recovery occurred in only one of five animals that were treated with an infusion of naloxone, 10 mg/kg/hour, and in none of five animals given 1 mg/kg as a bolus. Because these results are not related to any observed change in blood pressure, we believe that naloxone may be achieving its effect through the preservation of spinal cord blood flow, as well as other mechanisms that have yet to be defined.

Effect of naloxone on posttraumatic ischemia in experimental spinal contusion.

The effect of naloxone on blood flow and somatosensory evoked potentials was studied in cats subjected to 400 gm-cm contusion injuries of the thoracic spinal cord. Eight cats were treated with 10 mg/kg naloxone 45 to 60 minutes after injury, 11 cats were given 10 ml of saline instead of naloxone, and six cats were neither injured nor treated. Hydrogen clearance was used to measure blood flow in the lateral white columns at the contusion site. Naloxone, given intravenously, significantly inproved the blood flow rates in the lateral column white matter. At 2 hours after injury, the mean blood flow in the saline-treated cats fell to 50% (p greater than 0.01) of preinjury flow rates, whereas it increased 6% (p greater than 0.50) in naloxone-treated cats, and 12% (p greater than 0.50) in uninjured cats. At the 3rd hour after injury, the respective flows fell 47% (p less than 0.01), and 6% (p greater than 0.50), and increased 15% (p greater than 0.50) of the preinjury flow rates. The naloxone-treated cats had striking preservation of sensory function and somatosensory evoked potentials at 24 hours after injury. At 24 hours, responses had returned in all the naloxone-treated cats and in only 11% of the saline-treated cats. The probability of this combination of events occurring by chance is 0.0030. The authors conclude that naloxone may be useful for the treatment of spinal cord injury. The mechanism of the effect is unknown.

Effect of aminophylline and isoproterenol on spinal cord blood flow after impact injury.

A study of the effects of spinal cord injury upon spinal cord blood flow was carried out in cats. A 400 mg-cm impact produced an overall reduction in spinal cord blood flow of 24% in the white matter and 30% in the gray matter, as determined by 14C-antipyrine autoradiography. At the level of the injury, white-matter flow was 8.1 ml/100 gm/min, a reduction of 49%, and in the gray matter, 12.5 ml/100 gm/min, a reduction of 76%. Treatment with aminophylline and isoproterenol improved the overall blood flow in the spinal cord. At the level of the injury, white-matter flow after this treatment was no longer significantly different from control values. The gray-matter flow remained decreased to 26.2 ml/100 gm/min, a reduction of only 47%. It is proposed that aminophylline and isoproterenol may increase cyclic adenosine monophosphate (AMP) and prevent platelet aggregation along the endothelial surfaces of the microcirculation, and may thereby help to maintain improved perfusion of the injured spinal cord.

The role of the sympathetic nervous system in pressor responses induced by spinal injury.

Spinal cord injury consistently evokes a transient 3- to 4-minute rise is systemic pressure, followed by prolonged hypotension. Because the role of the sympathetic nervous system in these blood pressure changes is not clear, the pressure responses were studied using systematic ablation of the peripheral sympathetic nervous system. In total, 24 cats were subjected to bilateral thoracic sympathectomy, adrenalectomy, splanchnicectomy, combinations of the preceding, sham operation, or no treatment. Either 3 or 24 hours after the ablations, the blood pressure responses were evoked by 400 gm-cm contusions of the thoracic cord. Although neither thoracic sympathectomy nor adrenalectomy alone abolished the hypertensive phase, the combination of the two procedures did. This suggests that both the thoracic sympathetic ganglia and the adrenal glands participate in the pressor response. Thoracic sympathectomy affected primarily the early part, whereas adrenalectomy diminished the later part of the hypertensive response. This correlates with the function of the former being neurally and the latter being humorally mediated. None of the sympathetic lesions consistently affected the hypotensive phase. Spinal contusion injury produces widespread sympathetic activation, mediating the hypertensive changes.

Vestibulospinal monitoring in experimental spinal trauma.

Vestibulospinal tract function was monitored in experimental contusion of the spinal cord in cats, and compared with somatosensory cortical evoked potentials. Both white and gray matter portions of the vestibular and somatosensory pathways were evaluated in cord injuries at T-7 and L-4. Severe contusions of 20 gm-20 cm force impact resulted in a rapid (less than 1 second) abolition of thoracic white matter conductivity, but a somewhat slower (4 to 5 minutes) loss of lumbar gray matter responses. A paradoxical transient recovery of white matter conductivity occurred 1 to 2 hours after injury, despite eventual progression to central hemorrhagic necrosis at the contusion site. In contrast, mild contusions (20 gm-10 cm force impact) produced only a temporary loss of neuronal activity: white matter for 1 to 2 hours, and gray matter for 30 to 40 minutes. In general, vestibular and somatosensory potentials showed similar sensitivity to contusion, although the former tended to recover earlier. We conclude that contusion injury causes two types of neuronal dysfunction in spinal cord: 1) a low-threshold concussion-related loss of activity lasting 30 to 120 minutes; and 2) a higher threshold necrotic process, requiring 1 to 2 hours to develop, which apparently spreads from gray to white matter.

Ethanol potentiation of central nervous system trauma.

Two models have been used to study the effects of ethanol on injuries of the central nervous system. The spinal cords of cats were injured by delivering a 200 gm-cm impact to the exposed dura mater. A second group of animals received a similar injury to the exposed dura mater overlying the cerebral hemispheres. The animals were divided into two groups, those that received an infusion of ethanol before injury, and control animals that received no ethanol. The parameters of injury used in this model produced small and insignificant lesions in those animals that received no ethanol; however, when the animals were pretreated with ethanol, a considerable increase in the extent of the injury was noted. These include alterations in membranes-bound enzymes and clotting mechanisms, and alteration of cell membranes through abnormal free radical reactions.