Perfusion heart

The radioiodinated IPPA has been used for several years as a scintigraphic heart agent426. The metabolites of IPPA427 have been re-investigated recently428. The studies indicated the compounds 281-285 in rat-heart perfusates besides an ester of IPPA and IPPA itself. 

Recently, a family of monocationic complexes of the type [M(N)(P-N-P)-(S2CNR1R2)]+, which exhibit high myocardial uptake in rats, was also described [51,52]. Some of these complexes possess superior biological properties, compared with Sestamibi and Tetrafosmin. However, because of the possibility of species-dependent effects, further studies of these agents in other animal models are underway, in order to assess their utility as heart perfusion agents [52]. 

The following data were obtained for metabolite concentrations in a rat heart perfused with glucose ... 

A Banyu patent, which describes 203 compounds, highlights a very similar compound (example 50) (28) which is reported to show 87% inhibition at 1.1 //M of ET-1 binding in porcine aorta receptors, and activity in vitro in the guinea-pig trachea and on rat heart perfusion pressure. There is no other published information on this series of compounds. 

Chronic estrogens deficiency in overiectomized rats (3 weeks) resulted in impaired functional recovery in a perfused heart model of global ischemia and reperfusion while supplementation with estrogens improved the postischemic outcome6. However, estrogens replacement in ovariectomized female rats decreased the recovery of function in hearts perfused with palmitate.7 In aged overiectomized female rats, chronic estrogens replacement increased postischemic functional recovery in isolated rat hearts.8... 

The effects of hypertonic perfusion during hypoxia has been investigated in the Langendorff-perfused rabbit heart. During 60 min of control hypoxia (295 mosM), Na i rose from 22 to 100 meq kg dry weight whilst [Ca Ji rose from 347 to 1306 nM. In hearts perfused with 325 mosM buffer the increases in Na i and Ca j were reduced by 65 and 60%, respectively. Hypertonic perfusion also diminished Na" uptake after normoxic acidification by 87%. The role of creatine kinase (CK), high energy phosphates and Ca -influx in... 

Tsujita and Okuda demonstrated in vitro that lipoprotein lipase is capable of catalyzing FAEE synthesis (Tsujita. 1994a). Chang and Borensztajn supported this observation by demonstrating that FAEE synthesis in an isolated rat heart perfused with chylomicrons and ethanol is mediated by lipoprotein lipase (Chang, 1997). The basic characteristics of enzymes involved in FAEE synthesis is presented in Table 1. 

Schneider, J. A., Sperelakis, N. Eur. J. PharmacoL 27 (3), 349 (1974). Valinomycin blockade of slow channels in guinea pig hearts perfused with elevated D plus and isoproterenol... 

Kupriyanov et al. also noted an increase in [Na ] and a decrease in [K ]j in rat hearts perfused with 1 mM KCN. Decreased Na K ATPase activity due to decreased ATP levels could explain this change. However, it is reported that even a 20-fold decrease in cytoplasmic ATP/ADP does not decrease Na K ATPase activity in perfused rat heart, so the 5-fold decrease observed by Kupriyamov et al. cannot explain the increased [Na lj. These authors suggest that Na K ATPase is inhibited by the increased Pj, which can form a ternary abortive complex with the enzyme and ADR... 

For this, we assessed the role of NO in the isolated spontaneously beating heart perfused at constant flow in a Langendorff apparatus. As shown in Fig. 4, stimulation of the sympathetic nerves originting from the stellate ganglia (4 Hz for 10 sec ) in the rat heart elicited a marked increase in heart rate and NE overflow. Perfusion with various NO donors [i.e., SNP (0.1 and 1 fiM) and SIN-1 and SNAP (both at 10 fxM)] failed to affect the heart rate (Fig. 4A), but markedly decreased perfusion pressure (i.e., it caused... 

Isolated rabbit heart 5-HT depolarized post ganglionic neurons, which induced the release of noradrenaline and acetylcholine. In the isolated rabbit heart perfused by the Langerdorff technique in the presence of muscarinic antagonists, 5-HT dose-dependendy induced positive chronotropic and ionotropic effects which are selectively and competitively blocked by S-HTg receptor antagonists. 

Ugare 1. Utilisation of VLDL-TAG by working hearts prepared from control and endotoxic rats. Rats were pretieated with endotoxin prior to liver perfusion (VLDL preparation) or heart perfusion. Results are means SEM for n = 6-10 experiments, P < O.OS P < 0.01 compared to control hearts perfused with control VLDL. 

Hal, physiologically active) and tissue-residual (nascent) components and compared to NEFA-perfused hearts (Fig. 3). Total (heparin-releasable -l- tissue-residual) LPL activity was significantly increased in VLDL-perfused hearts compared to hearts perfused with NEFA (1.1 mM oleate) under identical conditions perfusion with endotoxic VLDL (VLDL-LPS) increased the proportion of the enzyme present at the endothelium (i.e. heparin-releasable) whilst decreasing the amount of residual enzyme in the tissue (i.e. causing translocation of the enzyme from intracellular to endothelial site) (Fig. 3). 

Halmosi R, Berente Z, Osz E et al. Effect of poly(ADP-ribose) polymerase inhibitors on the ischemia- reperfusion-induced oxidative cell damage and mitochon ial metabolism in Langendorff heart perfusion system. Mol Pharmacol 2001 59(6) 1497-1505. 

---