Protective effects of trifluoperazine on the microcirculation of cold-stored livers

Previous studies have shown a protective effect of trifluoperazine (TFP), a calmodulin inhibitor, upon the microcirculation of cold-stored kidneys. The present study points to similar beneficial effects of TFP on the microcirculation of cold-stored livers; 25 canine livers were preserved for 24 hr with Euro-Collins' solution (EC) (n = 8), University of Wisconsin solution (UW) (n = 7), or UW + TFP (n = 10). The stored livers underwent heterotopic transplantation (HLTX); hepatic-artery and portal-vein pressure and flow were monitored; oxygen consumption and extraction were measured before HLTX and at 15-min intervals after reperfusion, for 1 hr. Mean hepatic-artery and portal-vein flow (HAF & PVF) prior to donor hepatectomy were 172 and 530 cc/min, respectively. Poor HAF and PVF occurred in EC-HLTX (mean 35, 175 cc/min, respectively). The damaged EC-flushed livers could not compensate to the decreased hepatic blood flow by increased oxygen extraction (oxygen consumption and extraction, 8.7 vol.% and 48%, respectively). Light and electron microscopy showed severe liver necrosis and periportal hemorrhages. Improved hepatic-artery and portal-vein flows were seen in UW HLTX (105 and 254 cc/min), and oxygen consumption and extraction were 16.4 vol.% and 66%, respectively. Liver biopsy taken just before reperfusion revealed well-preserved liver architecture. Liver biopsy obtained 1 hr after reperfusion revealed marked edema of the portal triad, sinusoid congestion, and hemorrhage. Electron-microscopy biopsies obtained during reperfusion at 15-min intervals revealed severe vasospasm of the terminal hepatic arterioles and progressive damage to the liver microcirculation. The addition of TFP to the UW-flush solution resulted in excellent protection of the liver microcirculation. Marked increase in hepatic-artery and portal-vein blood flow was noted after reperfusion (mean 167 and 421 cc/min, respectively (P 0.02 vs. UW: P 0.001 vs. EC). The recovery of metabolic activity was evident by the high oxygen consumption and extraction (25.8 vol.% and 80%, respectively). And serial liver biopsies obtained after reperfusion have shown excellent protection of liver architecture and the absence of hepatic arteriolar vasospasm. Taken together, these data suggest that the addition of TFP to the UW solution protects the liver microcirculation by rendering the hepatic microcirculation insensitive to vasospastic stimuli during reperfusion, thus permitting better metabolic recovery after transplantation.     

Decayed, missing, and filled teeth among Jewish and Arab schoolchildren in Israel

The purpose of this investigation was to gather information on caries prevalence in schoolchildren of Arab and Jewish populations, and compare caries prevalence according to sex, age and population examined. Altogther, 3672 children were included in the survey (1975 Jews, 1001 of whom were females; and 1697 Arabs, 840 of whom were females). During the examination only dental caries were checked. Caries were marked according to the DMF index. Compared to former years there is an increase in the prevalence of caries throughout the population. A slightly lower caries prevalence was found among Jewish children than among Arab children of the same age. However, when DMF is broken down into its component parts, Arab children were seen to have a greater number of teeth affected by caries and in need of treatment (D). Furthermore, treatment need has been met to a much greater degree among Jewish children than among Arab children. Arab children received almost no dental care.     

The protective effect of calcium inhibitors and of captopril on the renal microcirculation during reperfusion

Reperfusion injury is increasingly recognized as a key factor in the development of posttransplant acute tubular necrosis. Previous studies have shown that addition of the calmodulin inhibitor trifluoperazine (TFP) to Collins' flush solution protected the cortical microcirculatory integrity and dramatically improved renal viability after transplantation. The present report describes the protective effect(s) of TFP in the course of reperfusion injury. Twenty mongrel dogs underwent bilateral nephrectomy; in each instance, the left kidney was flushed immediately with 250 ml of cold Collins' solution, and the right kidney was flushed with the same solution containing TFP, 5 mg/L. After 48 and 72 hr of preservation, each kidney was connected through silastic shunts to the femoral vessels of another dog. The mean renal blood flow (RBF) immediately after reperfusion was 2.2 ml/g/min and 1.7 ml/g/min in the left and right kidneys, respectively, and was similar to mean RBF measurements prior to nephrectomy. After 15 min of reperfusion, there was a sharp decrease in mean RBF in the Collins' flushed kidneys, which persisted after 60 min of reperfusion (0.37 ml/g/min). In contrast, there was only a mild decrease in mean RBF in the TFP-flushed kidneys (1.27 ml/g/min). A partial explanation for the favorable effect of TFP may be related to the inability of the ischemic cell to handle the increased calcium load associated with reperfusion (calcium paradox). In a test of this possibility, 0.5 mg/kg of verapamil, a calcium channel blocker, was infused during reperfusion. No beneficial effects of this drug were noted in either Collins' or TFP-flushed kidneys (n = 10). However, when 1.25 mg/kg of captopril, an angiotensin-converting enzyme inhibitor, was infused at the time of reperfusion, a dramatic amelioration of the reperfusion injury occurred in the Collins' flushed kidneys (1.2 ml/g/min) (n = 10). Taken together, these data suggest that the damage to cold-preserved kidneys flushed with Collins' solution alone may occur at the time of actual reperfusion. Such reperfusion damage is ameliorated by TFP and captopril. The known relationship between calcium and the effect of angiotensin on the vascular smooth muscle cell may explain in part the protective role of calcium inhibitors placed in preserved kidneys prior to reperfusion.