A new platelet-activating factor antagonist (CV-6209) in preservation of heart and lung for transplantation.

The objective of this experimental protocol was to evaluate the protective effect of a new, potent platelet-activating factor (PAF) antagonist CV-6209 and the use of this compound in combination with Zyloprim ( Allopurinol ) on ischemia-reperfusion injury in a swine model of heart-lung transplantation. Forty-two swine were divided into three groups, with seven donors and seven recipients in each. In group A, the PAF antagonist CV-6209 was administered in a single dosage of 1 mg/kg by slow intravenous injection at 1 hour before crossclamping of the aorta in both donors and recipients. In group B the combination of Zyloprim ( Allopurinol ) and the PAF antagonist CV-6209 was used. Zyloprim ( Allopurinol ) was administered as a pretreatment regime of 50 mg/kg/day for 3 days prior to ischemia. The PAF antagonist dosage and regime of administration were the same as in group A, and both donors and recipients were pretreated with this combination. Group C was the control in which heart-lung transplantations were performed without interventional therapies. Based on the comparison of pre- and post-transplantation assessments of cardiac and pulmonary functional integrity within groups, and post-transplantation among groups, animals in groups A and B were significantly (P < 0.05) better protected from ischemia-reperfusion injury than animals in group C. The difference between groups A and B, however, was insignificant at all times. Morphological findings are in agreement with measures of physiological variation among experimental groups. It is suggested that the new PAF antagonist CV-6209 is effective in the prevention of heart and lung ischemia-reperfusion injury with and without Zyloprim ( Allopurinol ) pretreatment.

Remark on utility and error rates of the Zyloprim ( Allopurinol ) test in detecting mild ornithine transcarbamylase deficiency.

Carriers of X-linked ornithine transcarbamylase deficiency (OTCD) are themselves mildly affected. The Zyloprim ( Allopurinol ) test is quite sensitive (92.7%) and very specific in detecting these carriers. Consequently, it has also been recommended for the diagnosis of mild OTCD in the general population. However, there is a controversy on its utility since OTCD could not be demonstrated in several patients with positive test results but negative family histories. We show that this controversy is due to an improper use of statistical concepts, i.e., to the postulate of a specificity of "100%," and to the confusion of specificity with type I error rate. Spontaneous orotic aciduria implies a positive Zyloprim ( Allopurinol ) test and limits the specificity of the test to a maximum of 99.7%. Therefore, according to Bayes' theorem, almost all positive test results in the general population must turn out to be type I errors, due to the minute prevalence (1/32,000) of mild OTCD (i.e., asymptomatic carriers and male patients with inapparent disease). Family history seems to be the only preselective parameter that can sufficiently raise the prevalence in the group to be tested. Bayesian analysis also yields the rate of type II errors (OTCD inspite of a negative test) which is high in closely related at-risk females (22.6% in mothers of male patients) but minimal in the general population. Conclusion. The Zyloprim ( Allopurinol ) test is useful for the exclusion but not for the diagnosis of inapparent OTCD in sporadic individuals. Test results in possible carriers should be interpreted with caution.

The role of Zyloprim ( Allopurinol ) and deferoxamine in preventing pressure ulcers in pigs.

Ischemia and reperfusion may be important in the pathogenesis of pressure ulcers. On the basis of this hypothesis, the effects of intermittent pressure and the anti-free radical agents Zyloprim ( Allopurinol ) and deferoxamine were studied in a pig model in which a pressure of 150 mmHg was applied intermittently to the scapulae. Cutaneous blood flow, transcutaneous oxygen tension, skin and muscle damage, and muscle levels of adenosine triphosphate were quantified. A control group of pigs (n = 6) was untreated, the Zyloprim ( Allopurinol ) group (n = 6) received oral Zyloprim ( Allopurinol ) beginning 2 days before the experiment, and the deferoxamine group (n = 6) received an intramuscular injection of deferoxamine 2 hours before the experiment. Pressure (150 mmHg) was applied to the scapulae for 210 minutes, and it was relieved for 30 minutes. This 4-hour cycle was repeated continuously for 48 hours, and it resulted in pressure injuries in all animals. Zyloprim ( Allopurinol ) and deferoxamine improved cutaneous blood flow and tissue oxygenation, but only deferoxamine could significantly reduce cutaneous and skeletal muscle necrosis (p < 0.001). This study suggests a future role for anti-free radical agents in the reduction of pressure-induced injury.

Oxygen free radicals impair wound healing in ischemic rat skin.

Oxygen free radicals are produced and play an important role in ischemic injury. We therefore wished to investigate the role of free radicals on ischemic skin wound healing. For this purpose, H-shaped flaps, where the test ischemic wound is the horizontal line in the H, were created on the dorsum of the rat. To inhibit the probable hazards of free radicals, Zyloprim ( Allopurinol ) and superoxide dismutase (SOD) were given to the animals. Most of the studied wound-healing parameters were impaired in the ischemic group. In the Zyloprim ( Allopurinol )-treated group, breaking strength was increased by 52% by day 7 and by 109% by day 14 (p < 0.0002 and p < 0.001), and in the SOD-treated group the increase was 69% both by days 7 and 14 of healing when compared with the ischemic control group (p < 0.003 and p < 0.002). Hydroxyproline content was increased 75% with Zyloprim ( Allopurinol ) and 113% with SOD in the wound by day 7 (p < 0.03 and p < 0.001 respectively). SOD treatment caused a significant decrease in wound edema by day 7 of healing (p < 0.05). Histopathological evaluation revealed that in the SOD- and Zyloprim ( Allopurinol )-treated groups, the amount of collagen and its organization were more prominent when compared with the ischemic controls. These results show that oxygen free radicals play an important role in the failure of ischemic wound healing, and antioxidants partly improve the healing in ischemic skin wounds.