fMet-Leu-Phe receptor expression by an interstitial cell in rabbit right atrium following left ventricular myocardial infarction.

Previous studies have shown that rabbit hearts subjected to in vivo left ventricular myocardial infarction and subsequent ex vivo perfusion respond to N-formylmethionyl-leucyl-phenylalanine (fMLP) with enhanced eicosanoid synthesis. This synthetic response occurs primarily in the right cardiac atrium, a site distant from the injury, and is not the result of increased enzymatic capacity for arachidonate metabolism. To further investigate the mechanism of this enhanced synthetic response, [3H]fMLP binding was characterized and binding sites were localized autoradiographically in intact tissue sections prepared from control hearts and hearts subjected to left ventricular myocardial infarction (1, 2, and 4 days postinfarction). Analysis of binding isotherms revealed a saturable high affinity (KD approximately 1 nM) fMLP binding site in the right cardiac atrium. After myocardial infarction specific binding in right atria (2 day) increased 12-fold (Bmax = 14.8 +/- 2.4 fmol/cm2) compared with normal controls (Bmax = 1.2 +/- 0.1 fmol/cm2). Specific binding of fMLP also increased in the infarcted zone of left ventricle, but Bmax was only 30-50% that of right atria. Light microscopic autoradiography studies revealed that atrial fMLP binding sites were highly concentrated in small morphologically undifferentiated cells located in interstitial and perivascular spaces. These results demonstrate the existence of a formylated peptide receptor on a nonleukocytic cell and illustrate its regulation following left ventricular injury.

Role of invading leukocytes in enhanced atrial eicosanoid production following rabbit left ventricular myocardial infarction.

The isolated perfused hearts of rabbits previously subjected to in vivo left ventricular myocardial infarction (LVMI) show a 5-10-fold increase in f-Met-Leu-Phe (FMLP) and bradykinin (BK)-stimulated eicosanoid metabolite production relative to noninfarcted hearts. This exaggerated arachidonate metabolism has been shown to occur primarily in the cardiac atria, a site remote from the zone of injury and to be associated with a 10-15-fold increase in atrial FMLP receptor number in the absence of atrial inflammation. All of these changes were temporally related to leukocyte infiltration into the infarct zone. To determine whether invading leukocytes mediate these responses, acute inflammatory cell influx was suppressed either by inducing leukopenia with nitrogen mustard or by administration of BW-755C, a mixed cyclooxygenase-lipoxygenase inhibitor. Both pharmacological manipulations resulted in a decrease in inflammatory cells in the infarct zone and a marked suppression (50-70%) of ex vivo agonist-stimulated eicosanoid metabolite production from perfused hearts and isolated atria. These manipulations also resulted in reversal of ex vivo FMLP-induced coronary vasoconstriction as well as augmentation of BK-induced coronary vasodilation. Further studies in nitrogen mustard-treated animals revealed a suppression of the LVMI-stimulated increase in atrial FMLP receptor number. These data show that suppression of leukocyte invasion after LVMI attenuates enhanced cardiac and atrial eicosanoid metabolite production, and results in marked changes in coronary vascular reactivity. An additional finding was that basal and stimulated LTB4 production was markedly increased in infarcted hearts. In vivo suppression of the increase in LTB4 production by BW-755C was associated with inhibition of inflammatory cell influx into the infarct zone. It therefore appears that LTB4 may be an important proinflammatory mediator of leukocyte invasion after LVMI.

Exaggerated atrial arachidonate metabolism in rabbit left ventricular myocardial infarction.

Isolated perfused rabbit hearts that have previously been subjected to in vivo left ventricular myocardial infarction respond to N-formylmethionyl-leucyl-phenylalanine (fMLP) or bradykinin (BK) administration with the synthesis of large quantities of eicosanoids. To anatomically localize these synthetic responses we studied the effects of fMLP and BK on eicosanoid synthesis in isolated atria and isolated perfused ventricles from normal and infarcted (4 d in vivo) rabbit hearts. These studies revealed that enhanced agonist-stimulated eicosanoid synthesis occurs largely in the right atria of infarcted hearts, a site distant from the zone of injury. Studies of exogenous arachidonate metabolism in microsomes prepared from various regions of the heart showed that while prostaglandin synthetic capacity is preferentially localized to the right atrium, right atria from normal and infarcted hearts have similar thromboxane and PGE2 synthetic capacity. These results demonstrate that enhanced agonist-stimulated eicosanoid synthesis following rabbit left ventricular myocardial infarction occurs largely in the right atrium, and that this effect is independent of the activity of prostaglandin synthetic enzymes.

Genesis of morphologically identified neurons in the dorsal lateral geniculate nucleus of the cat.

Neurons in the dorsal lateral geniculate nucleus of the cat can be grouped into five morphological classes based on a variety of structural characteristics. These same structural characteristics can serve as morphological signatures for the three physiological classes (X, Y, W) of neurons found in this nucleus. The purpose of this study was to determine if a relationship exists between the birthdate of neurons within the dorsal lateral geniculate nucleus and the adult morphology of those neurons. Seven cats, each of which had received a single injection of 3H-thymidine, were studied. A total of 2,138 Golgi-impregnated neurons were identified in the dorsal lateral geniculate nuclei of these seven cats; 1,517 of these neurons were successfully resectioned and recovered, of which 385 (25%) were found to contain the 3H label. Neurons from each of the five morphological classes were labeled in each of the six animals that received a 3H-thymidine injection between embryonic day 24 (E24) and E28. Class 3 and class 5 neurons were labeled in a cat injected with 3H-thymidine on E30. These findings demonstrate that the development of the morphological class of a neuron in the dorsal lateral geniculate nucleus is independent of the time of its final cell division. Further, given the relationship that exists in the cat's dorsal lateral geniculate nucleus between neuronal structure and function, the present findings suggest that the different physiological classes of cells found in this nucleus undergo their final cell divisions throughout most of the period of neurogenesis except that the functional role of neurons born late in this period may be more restricted.