No abstract

The causal relationship between intracellular Ca2+ overloading and reperfusion-induced contracture was examined from changes in intracellular Ca2+ concentration ([Ca2+]i) at rest, changes in the magnitude and time course of intracellular Ca2+ transients, and the development of contracture. Single myocytes isolated from guinea pig hearts were subjected to the conditions mimicking ischemia and reperfusion. Ischemic condition was produced by superfusing myocytes with hypoxic substrate-free solutions containing elevated concentrations of K+, H+, and lactate as described by Ferrier et al. (Circ. Res. 56: 184-194, 1985). Changes in [Ca2+]i were estimated using fura-2 as the Ca2+ indicator. Under these conditions, twitch contractions were suppressed during simulated ischemia associated with an early and gradual rise of [Ca2+]i. The development of contracture, however, was not observed. Upon "reperfusion" of myocytes that had been subjected to 20 min of the above "ischemic" condition, the elevated [Ca2+]i declined rapidly. With the recovery of twitch contractions, contracture developed despite a substantial decrease in [Ca2+]i. These results indicate that reperfusion-induced contracture is not associated with a concomitant increase in [Ca2+]i in isolated myocytes.

No abstract

Initial experiments were designed to determine if vasoactive concentrations of nitric oxide (NO) alter contractility in rat heart. Contractile function was monitored in left atrial and papillary muscles (30 degrees C; paced at 0.5 Hz) during cumulative addition of 3-morpholino-sydnonimine-HCl(SIN-1), an agent that releases NO. At concentrations between 10(-7) and 10(-4) M (NO concentrations of approximately 10(-8)- 3 x 10(-7) M), SIN-1 did not affect contractility in either tissue. Similarly, 10(-4) M SIN-1 did not alter the positive inotropic responses to isoproterenol or increasing extracellular [Ca+2] ([Ca+2]o). To obtain higher concentrations of NO, additional studies were conducted using authentic NO. NO-saturated stock solutions and a corresponding control solvent were adjusted to pH 1.6 with HCl. Dose-dependent effects of NO were examined by adding aliquots of the stock solutions (or control solvent) to the bathing solution. At final concentrations of 1 x 10(-5)- 5 x 10(-4) M, NO produced transient, concentration-dependent decreases in contractility that were paralleled by reductions in buffer pH. Control solvent elicited similar reductions in pHo and transient decreases in contractility; however, the negative inotropic action elicited by the NO-containing solution was approximately 20% greater than that observed in control conditions. These data demonstrate that only high concentrations of NO depress contractility in isolated rat cardiac muscle, and suggest that this effect is mediated by both acidosis and a pHo-independent mechanism.

ABSTRACT. A 7-year-old, male, mixed breed dog was referred to the Veterinary Teaching Hospital at Kitasato University because of anorexia, lameness and multiple cutaneous lesions. Observation of bone marrow plasmacytosis, osteolytic bone lesions, serum myeloma protein and cutaneous infiltration of myeloma cells led us to a diagnosis of multiple myeloma (MM) with cutaneous involvement. Polymerase chain reaction and sequence analysis for the rearranged genes of immunoglobulin and T-cell receptor demonstrated that the neoplastic cells found in skin lesions or bone marrow are of B-lymphocyte lineage and share a common original precursor cell. The dog was treated with UW-Madison protocol or melphalan/prednisone protocol and survived 175 days. This is rare case of anaplastic MM with cutaneous involvement in dog.