At 1-2 h after intragastric administration of ketoconazole, a cytochrome P-450 inhibitor, to rats, there was a 50-60% decrease in the activity of hepatic 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase. Inhibition reached a maximum at 6-12 h after the drug was given, but after 24 h enzyme activity was stimulated by 60%. The rates of synthesis of hepatic non-saponifiable lipids in vivo showed a similar time-dependent pattern of change. During the first few hours after drug administration, the hepatic cytochrome P-450-dependent metabolism of lanosterol was suppressed in vivo. However, 24 h after treatment, this activity was stimulated, an effect which was also observed by pre-treatment of the rats with the drug for several days. Suppression of hepatic HMG-CoA reductase and lanosterol 14 alpha-demethylase activities was accompanied by a relative increase in the accumulation of labelled polar sterols in the liver in vivo. In the intestine, ketoconazole also resulted in a rapid decline in the rate of synthesis of non-saponifiable lipids and an inhibition of lanosterol 14 alpha-demethylation in vivo. However, in contrast with the liver, there was no stimulation of non-saponifiable lipid synthesis after 24 h.
In rats fed on a diet containing 1% cholesterol for 24 h, the decrease in hepatic non-saponifiable lipid synthesis, cholesterogenesis and 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase activity was accompanied by an increase in the proportion of newly synthesized polar sterols in vivo. In these animals there was also a strong inverse correlation between the proportion of polar sterols in the non-saponifiable lipid and hepatic HMG-CoA reductase activity. A similar correlation was not observed in animals fed on a normal diet. Cholesterogenesis in the intestine was not as sensitive to inhibition by dietary cholesterol as was that in the liver, and there was no increase in the polar-sterol content of the newly synthesized non-saponifiable-lipid fraction.
Background Donation after Circulatory death is gaining worldwide acceptance. Most protocols regard their first cases to be performed with donor and recipient in the same institution. Few records of children or distant procurement have been published. Methods Our institution was offered a heart from a 3‐day‐old, 3.4‐kg child, blood group A, suffering irreversible encephalopathy. Parents accepted withdrawal of life‐sustaining therapy and agreed to donation. The donor hospital was located 340 km away. Concomitantly, a 2‐month‐old, 3.1 kg, blood group type B and with non‐compaction ventricles was awaiting for the heart transplant in our unit. Results Thirty‐seven minutes after withdrawal of life‐sustaining therapy, the heart arrested. Five minutes afterwards, a sternotomy was performed. The supra‐aortic vessels were clamped altogether. Aorta and right appendage were cannulated and connected to heart‐lung machine. The innominate artery above the clamp was severed. The heart resumed spontaneous rhythm in less than 1 min. Ventilation was restored and extracorporeal circulation was maintained for 32 min. Upon cardiologic arrest, the graft was harvested as routinely. The heart was cold‐stored and transported by plane to our Hospital. An orthotopic bicaval transplant was performed. Overall cold ischaemia was 245 min. Ten weeks later, the child was discharged home in good condition. Conclusion Donation in circulatory death could increase the pool in neonates. Extracorporeal circulation proves successful for procurement in neonates. Distant procurement plus cold storage for donation in circulatory death is feasible. Donation in circulatory death and ABO non‐compatible strategies are complementary to each other.
Background: Collaboration between cardiac surgeons and cardiologists can offer interventions that each specialist may not be able to offer on their own. This type of collaboration has been demonstrated with the hybrid Stage I in patients with hypoplastic heart syndrome. Since that time, a hybrid approach to cardiac interventions has been expanded to an incredible variety of potential indications.Methods: Seventy-one patients were scheduled for a hybrid procedure along 8 years. This was defined as close collaboration between surgeon and cardiologist working together in the same room, either cath-lab (27 patients) or theater (44 patients).Results: Six groups were arbitrarily defined. A: vascular cut-down in the cath-lab (27 neonates); B: bilateral banding (plus ductal stent) in hypoplastic left heart syndrome or alike (15 children); C: perventricular closure of muscular ventricular septal defect (10 cases); D: balloon/stenting of pulmonary branches along with major surgical procedure (12 kids); E: surgical implantation of Melody valve (six patients) and others (F, one case). Two complications were recorded: left ventricular free wall puncture and previous conduit tearing. Both drawbacks were successfully sort out under cardiopulmonary by-pass.Conclusion: Surgeon and cardiologist partnership can succeed where their isolated endeavors are not enough. Hybrid procedures keep on spreading, overcoming initial expectations. As a bridge to biventricular repair or transplant, bilateral banding plus ductal stent sounds interesting. Novel indications can be classified into different groups. Hybrid procedures are not complication-free.
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