Percutaneous (nonsurgical) supported angioplasty in unprotected left main disease and severe left ventricular dysfunction.

A 69-year-old patient with the equivalent of severe, unprotected left main coronary artery disease associated with marked left ventricular dysfunction with ventricular aneurysm who had Class IV angina, underwent supported angioplasty utilizing a total percutaneous approach. The patient tolerated occlusion of his main left coronary artery for a total of 7 minutes without difficulty, during dilatation of left anterior descending and two circumflex lesions. He was discharged the following day, symptom free.

[The effect of activated lymphocytes on cardiac contractility]. / Efecto de linfocitos activados sobre la contractilidad cardíaca.

Activated lymphocytes may have potent biologic effects outside the frame of the immune system. In these studies we analyzed the interaction of activated normal human lymphocytes and/or soluble products of lymphocyte activation on the contractile activity of isolated rat atria. The results indicate that phytohemagglutinin activated lymphocytes of the CD4 phenotype exert a positive inotropic effect on spontaneously beating atria. This effect is linked to steps of lymphocyte activation that precede cell division. Soluble factors released to the supernatant of stimulated lymphocytes can substitute for the intact cells. Interleukin-2 (IL-2) appears to be an important component of the active supernatants, as their activity can be reduced by monoclonal anti-IL-2 or by preincubation of the heart tissue with monoclonal anti-IL-2 receptor (anti-Tac). Highly purified IL-2 was active at 10 units/ml. In order to induce a positive inotropic effect at lower doses of natural or recombinant IL-2 (2-3 units/ml), synergic factors were required (2 x 10(-6) M arachidonic acid, AA, or Ca ionophore A 23187). Indirect evidence indicates that IL-2 exerts its biologic effect by turning on the phosphoinositide cycle and activating protein kinase C in the heart tissue target. It is postulated that similar mechanisms may be activated in inflammatory myocardiopathies or during the treatment of cancer with massive doses of IL-2.

Lymphocyte-induced stimulation of the contractile response of the heart.

In previous reports we have shown that phytohemagglutinin (PHA)-activated human lymphocytes had positive inotropic effects on spontaneously beating isolated rat atria. In this study, we demonstrated that the stimulatory effect on heart contractility induced by lymphocytes was linked to early events of lymphocyte activation by lectins. Active soluble factors were gradually released to the fluid phase. Similar results were obtained with both mitogenic (PHA) and nonmitogenic (WGA) lectins indicating that the stimulatory action of activated lymphocytes did not require cell division. Absence of Ca2+ inhibited both the generation of the stimulatory activity and lymphocyte proliferation. In contrast, verapamil, dexamethasone and low concentrations of cycloheximide eliminated only the appearance of the stimulatory effect.

Stimulation of heart contractility by supernatants from lectin-activated lymphocytes. Role of IL-2.

The positive inotropic effect of cell-free supernatants from lectin-activated lymphocytes is lost by dialysis and can be partially restored by addition of arachidonic acid (AA). Interleukin-2 (IL-2) in the presence of AA could stimulate the response of the heart while the interferons (alpha-IFN or gamma-IFN) were ineffective. The activity of PHA-L-SN and that of IL-2 + AA was neutralized by anti-IL-2 MAb. These results suggest a key role for IL-2 in the stimulation of heart contractility by supernatants from activated lymphocytes.

Reversal of immune complex inhibition of antibody-dependent cell-mediated cytotoxicity by normal human serum.

The results of this study demonstrate that inhibition of antibody-dependent cell-mediated cytotoxicity (ADCC) of human peripheral blood mononuclear cells (PBMC) by ovalbumin (OA)-IgG anti-OA immune complexes (IC) can be reversed by normal human serum (NHS) or serum from a patient with congenital deficiency of the second component of complement (C2 def-HS) lacking activity of the classical complement (C) pathway. On the other hand, NHS that had been inactivated by heating at 56 degrees C for 30 min (HI-NHS) or NHS depleted of the alternative C pathway activity by absorption with zymosan (Zy-NHS) did not restore the ADCC of IC-blocked PBMC. These results suggest that the alternative pathway of C plays a very important role in the re-establishment of ADCC of PBMC blocked with IC. The recovered activity was susceptible to a new inhibition when re-exposed to IC, demonstrating that the NHS effect depends on the recovery of the functional activity of the receptor for the FC fragment of IgG on PBMC and not on the induction of non-specific cytotoxicity. The ability of NHS to restore the cytolytic potential of IC-inhibited PBMC was dependent on the time of exposure of PBMC to IC before the addition of the unblocking agent (NHS). After prolonged reaction of PBMC with IC, the blocked cells were unable to recover their ADCC activity by incubation with NHS. Unblocking of the Fc receptor of PBMC by C may be a physiological way to prevent permanent impairment of the immune mechanisms that depend on its function in the free state.

Positive inotropic effect of interleukin-2. Role of phospholipases and protein kinase C.

Recently, we have shown that soluble factors released by human lymphocytes after lectin stimulation could increase the contractile tension of rat atria "in vitro" and that interleukin-2 (IL-2) could be part of this reaction. The effect of IL-2 was potentiated by the Ca2+ ionophore A23187 or free arachidonic acid (AA). In this study we demonstrate that the action of IL-2 can be prevented by pre-incubation of the heart tissue with monoclonal anti-IL-2 receptor (anti-p55), suggesting that binding to the IL-2 receptor is necessary for the induction of the biologic effect. In the presence of A23187 or AA, the effect of the synthetic diacylglyceride oleoyl-acetyl-glycerol (OAG) was similar to that of IL-2. Elimination of phospholipase C activity by pre-incubation of the atria with 2-nitro-carboxyphenyl,N,N'-diphenylcarbamate (NCDC) abrogated the effects of IL-2 in the presence of A23187 or AA, but was ineffective when OAG + A23187 or OAG + AA was used. Inhibition of atrial phospholipase A2 activity with p-bromo-phenacylbromide (BPB) blocked the response of atria to either IL-2 + A23187 or OAG + A23187 but was not effective when AA was used as second signal (IL-2 + AA or OAG + AA). Both the OAG and the IL-2 positive inotropic effects could be prevented by the protein kinase C inhibitor 1-(5-isoquinolinesulfonyl)-2-methyl-piperazine (H7) but were poorly inhibited by N-(2-guanidinoethyl)-5-isoquinolinesulfonamide (HA1004), an inhibitor of the cyclic nucleotide-dependent protein kinases.(ABSTRACT TRUNCATED AT 250 WORDS)

Production of thromboxanes by transformed lymphocytes--effect on heart contractility.

We studied the effect of transformed lymphocytes from patients with chronic lymphocytic leukaemia (CLL) and the Raji cell (Raji) on the response of rat isolated atria to sodium arachidonate (AA). In contrast to normal lymphocytes, CLL cells and Raji cells decrease the contractile tension of rat isolated atria. Addition of exogenous AA (1.98 X 10(-6) M) to Raji, further reduced the isometric developed tension. Time of culture of Raji was important, as the negative inotropic effect was greater at 72 h than at 24 h of culture. Living cells were required and cell-free supernatants were inactive. Preincubation of CLL cells or Raji with cyclooxygenase inhibitors (acetyl salycilic acid, indomethacin) or inhibitors of thromboxane (TX) synthesis (imidazole, L-8027) abolished the negative inotropic response suggesting the contribution of TXs. L-8027 also reduced the growth rate of Raji cells, indicating that TXs may play a role in the regulation of cell division. The production of TXs by CLL and Raji cells from both endogenous and exogenous sources provided additional support to this hypothesis and suggested that activation of this metabolic pathway may be related to cell transformation.