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The study of adult human ventricular cells has been limited by tissue availability. In this study we describe techniques for the isolation of Ca(2+)-tolerant adult human ventricular cells from both transvenous endomyocardial and epicardial biopsies. Ca(2+)-tolerant cells were obtained from 80% of the biopsies processed. Although the yield of Ca(2+)-tolerant myocytes from either type of biopsy was low (1-5%), myocytes with normal resting potentials and action potentials can be obtained from single biopsy specimens, providing a source of normal human myocytes for electrophysiological study. Resting potentials (Vrest) were recorded in 41 isolated right ventricular endomyocardial cells at 37 degrees C. Sixteen cells were depolarized (Vrest = -26 +/- 13 mV), and 25 cells had normal resting potentials (Vrest = -84 +/- 6 mV). Action potentials were recorded in 16 cells. At a pacing cycle length of 1 s, 4 cells had prolonged action potential duration at 90% (APD90, 718 +/- 26 ms) and 10 cells had normal APD90 (381 +/- 94 ms) compared with those recorded from intact right ventricular septal trabeculae from explanted hearts. Voltage-clamp studies of isolated human ventricular myocytes obtained from these biopsies document the presence of currents previously reported from cells isolated from explanted hearts.

We conclude that OPC-8490 produces selective positive inotropic effects because of type III PDE inhibition combined with ion channel effects, with the latter property inhibiting the positive chronotropic response usually associated with agents that increase intracellular cAMP concentrations.

The prognosis of tetralogy of Fallot (TOF) treated only with Blalock-Taussig shunt (BTS) operation is unclear. A woman with TOF underwent classic BTS operation at 10 years of age. Despite no medication, she delivered two children and worked without apparent heart failure. At 72 years of age, she complained of dyspnea on exertion and leg edema. The cardiac angiogram revealed a well-patent BTS and severely stenotic right ventricular outflow tract. Right heart catheterization showed adequately maintained pulmonary blood flow with slight pulmonary arterial hypertension. Her unexpected yet favorable outcome reaffirms the importance of structural and functional self-adaptation even with cyanosis. If she had undergone a valve-sparing corrective surgery in adolescence, much better quality of life and outcome could have been expected.

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