Perfused heart preparations

The smallest sequence possessing most of the neurotensin spectmm of activities and its high potency is the hexapeptide C-terminus (1). [D-Trp ]-Neurotensin acts like a neurotensin antagonist in perfused heart preparations, but acts like a full agonist in guinea pig atria and rat stomach strips (122). 

Sugiyama, A., Kobayashi, M., Tsujimoto, G., Motomura, S., and Hashimoto, K., The first demonstration of CGRP-immunoreactive fibers in canine hearts coronary vasodilator, inotropic and chronotropic effects of CGRP in canine isolated, blood-perfused heart preparations, Jpn. J. Pharmacol, 50, 421-427, 1989. 

Efforts to predict the risk of potential QT prolongation over the last decade have resulted in the number of preclinical in vitro and in vivo methodologies. In vitro methods to predict QT liabilities range from simple recombinant cellular assays to disaggregated cells, isolated tissues and perfused heart preparations." ... 

Many studies have been performed in order to compare the mode of action, and retention kinetics in the myocardium, and the way of excretion of these different cationic species for both cell cultures, as well as in whole heart preparations. Even Tc NMR spectroscopy has been used to characterize in vivo the nature of the compounds for sestamibi (see Section 5.2.2.10.1). A recent comparative kinetic study between the different cations can be taken as a base for the clinical interpretation of the different perfusion imaging findings. ... 

Figure 2.16. The effect of change in flux through the glycolytic path (low vs high work rates) for two (A trout muscle B rat gastrocnemius) skeletal muscle systems in vivo (modified from Hochachka, 1994) and (C) for perfused rat heart preparations in vitro (modified from Kashiwaya et al., 1994). One of the instructive insights arising from these kinds of studies is the so-called [s] stability paradox remarkably stable concentrations of pathway intermediates during changes in pathway fluxes that can approach or exceed 100-fold. See text for other details.

Mesenteric artery was studied in the B and D KOs (Table 3). The B KO had no change in PE EC50 or maximum in rings, whereas the D KO had a decreased pressor response to PE in an isolated mesenteric bed preparation (3,7). This evidence for the D in mesenteric arteries fits binding data in WT mice (22a). Carotid and tail artery rings from the B KO had no change in PE effects, except that the carotid from the B KO was more sensitive to PE (7). Coronary arteries were studied in the D and AB KOs by examining coronary flow or pressure in the isolated perfused heart (16,18). Both studies pointed to a role of the D in coronary... 

Isolated working heart preparation Perfusion of the heart ex vivo through the left atrium and ejection via the aorta resembling physiological conditions. Measurement of cardiac output. Preload and afterload can be adjusted. Other characteristics similar to Langendorff preparation. 

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. 

Studies of the effect of muscle in vitro have included a variety of preparations, namely, heart-lung preparations, perfused limbs, perfused heart, and diaphragm. All these biological systems differ by the relative amount of muscle tissue in the preparation. 

Over the past decade, we (Sagawa, 1978) have measured the ventricular pressure (P)-volume (V) relationship in an isolated and blood perfused canine heart preparation and came to consider that the ventricular end-systolic P-V relationship (ESPVR) is (a) linear as opposed to the highly nonlinear P-V relationship of the frog s ventricle reported by Otto Frank a century ago, (b) rather insensitive to the preload and afterload and (c) changes its slope (E, ) sensitively with inotropic interventions without a significant shift in the volume intercept (Vq). This is to say that our model of the ventricle merely consists of a linear volume elastance E which varies with each heart beat from a smaller end-diastolic value to a larger... 

The cardiovascular actions of ellipticine in the dog and monkey have been studied low doses of the drug, 10-18 mg/kg i.v. in the dog, 5-20 mg/kg i.v. in the monkey and 6-25-18-75 mg in the isolated blood-perfused dog s heart, appeared to stimulate beta receptors and this would be prevented by pretreatment with reserpine and (+ )-propanolol, but not (-(-)-propanolol. Higher doses produced a non cific depression of the cardiac function in the isolated heart preparation and the intact animals [116a]. 

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