Atrial contractile abnormalities are common clinical disorders but few pharmacological models can reliably produce such abnormalities in isolated atrial muscle. Since sarcoplasmic reticulum (SR) calcium leak may underlie these contractile irregularities, we investigated whether 2-aminoethoxydiphenyl borate (2-APB), a calcium leak-inducer, affects mechanical function in isolated, superfused rat left atria. Exposing left atria paced at 3 Hz to >10 microM 2-APB produced sporadic mechanical events that occurred in the absence of pacing stimulus. Prolonging atrial diastole in the presence of 2-APB produced spontaneous mechanical activity (SMA) defined as numerous mechanical events occurring in the absence of pacing stimulus. SMA depends on atrial sodium and chloride gradients as decreasing superfusate concentration of either ion suppressed SMA. Increasing superfusate potassium to produce an EK of approximately -74mV reversed SMA, revealing possible membrane potential sensitivity. Mechanical function decreased with time in left atria treated with 2-APB and low sodium or the anion transport inhibitor 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) compared with atria exposed to low sodium or DIDS alone, suggesting 2-APB may decrease left atrial SR activator calcium. Thus, 2-APB produces instability in regular left atrial mechanical activity that may require forward-mode sodium-calcium exchange and chloride channel activities. This data identify a new model for studying atrial contractile abnormalities.
A simplified scheme for interpretation of urinary hippuric acid excretion data in terms of consecutive irreversible first-order processes is presented. The rate of excretion of endogenous hippuric, uric, and glucuronic acids is constant under the conditions of the experiments. The average value for the excretion constant KE for exogenous hippuric acid has been determined to be 2.7 hr-1 (0.0452 min-1) for doses of sodium hippurate ranging from 1 to 4 mEq. The average Ks for synthesis of hippurate from benzoate is 10.5 hr-1 (0.175 min-1) for doses of sodium benzoate ranging from 1 to 4 mEq. Study of 17 patients with varying degrees of renal disease as confirmed by standard p-aminohippurate and inulin clearances indicates that the determination of KE may be of value in the study of renal function, particularly where standard clearance techniques are not available. Preliminary data indicate that Ks may be useful in the study of the delay in synthesis of hippurate from benzoate that has been observed in some cases of liver pathology. Submitted on August 29, 1960
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