Background: The novel SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is responsible for the global coronavirus disease 2019 pandemic. Small studies have shown a potential benefit of chloroquine/hydroxychloroquine±azithromycin for the treatment of coronavirus disease 2019. Use of these medications alone, or in combination, can lead to a prolongation of the QT interval, possibly increasing the risk of Torsade de pointes and sudden cardiac death. Methods: Hospitalized patients treated with chloroquine/hydroxychloroquine±azithromycin from March 1 to the 23 at 3 hospitals within the Northwell Health system were included in this prospective, observational study. Serial assessments of the QT interval were performed. The primary outcome was QT prolongation resulting in Torsade de pointes. Secondary outcomes included QT prolongation, the need to prematurely discontinue any of the medications due to QT prolongation, and arrhythmogenic death. Results: Two hundred one patients were treated for coronavirus disease 2019 with chloroquine/hydroxychloroquine. Ten patients (5.0%) received chloroquine, 191 (95.0%) received hydroxychloroquine, and 119 (59.2%) also received azithromycin. The primary outcome of torsade de pointes was not observed in the entire population. Baseline corrected QT interval intervals did not differ between patients treated with chloroquine/hydroxychloroquine (monotherapy group) versus those treated with combination group (chloroquine/hydroxychloroquine and azithromycin; 440.6±24.9 versus 439.9±24.7 ms, P =0.834). The maximum corrected QT interval during treatment was significantly longer in the combination group versus the monotherapy group (470.4±45.0 ms versus 453.3±37.0 ms, P =0.004). Seven patients (3.5%) required discontinuation of these medications due to corrected QT interval prolongation. No arrhythmogenic deaths were reported. Conclusions: In the largest reported cohort of coronavirus disease 2019 patients to date treated with chloroquine/hydroxychloroquine±azithromycin, no instances of Torsade de pointes, or arrhythmogenic death were reported. Although use of these medications resulted in QT prolongation, clinicians seldomly needed to discontinue therapy. Further study of the need for QT interval monitoring is needed before final recommendations can be made.

A method is presented that consistently yields a large number of calcium-tolerant myocytes from mammalian, amphibian, and elasmobranch hearts and from mammalian stomach. The use of incubating solutions or cell harvesting techniques was not required. The time needed to isolate cells was shorter than previously reported values. Action potentials recorded from each cell type appear similar in configuration to that of the intact multicellular tissue. The isolated myocytes appear to tolerate long periods of electrophysiological experimentation using the "giga-seal" suction electrode technique of Hamill et al. (Pfluegers Arch. 391: 85-100, 1981). This method is ideally suited for comparative electrophysiological studies, since the procedure for cell isolation was not seriously modified according to the preparation or species used.

In cardiac muscle, Ca2+ plays a key role in regulation of numerous processes, including generation of the action potential and development of tension. The entry of Ca21 into the cell is regulated primarily by voltage-gated channels in the membrane. Until recently, it was felt that only one type of Ca2+ channel existed in cardiac ventricular muscle. Experiments reported here suggest that in isolated guinea pig ventricular myocytes, there are two distinct types of Ca2+ channels with markedly different activation thresholds, inactivation kinetics, and sensitivities to inorganic and organic Ca2+ channel blockers. The channels were also distinguished based on their response to increased frequency of clamping such that the current through the low-threshold channel decreased while that through the high-threshold channel increased. In a few cells, the current through both channels was enhanced by isoproterenol, a J3-adrenergic agonist, but only the high-threshold channel was enhanced by the Ca2+-channel agonist Bay K 8644. Thus, isolated guinea pig ventricular myocytes appear to have two types of Ca2+ channels distinguished by various criteria.In amphibian and mammalian cardiac muscle, a slow inward current (Iji) capable of transporting either Ca2l or Na+ has been identified (1-4). This current, which activates near -30 mV and inactivates slowly with two time constants (5, 6), appears to contribute to the maintenance of the plateau of the cardiac action potential and to the generation of tension. Recently, evidence for two distinct populations of Caa2+ channels has been put forward in a wide variety ofnoncardiac cells, including starfish eggs (7), pituitary cells (8), dorsal root ganglion neurons (9, 10), fresh water ciliates (11), and polychaete eggs (12). The biological grounds for the development of two types of calcium channels in the same neuronal cell, however, are not as yet clear. In cardiac muscle, the presence of two types of calcium channels may play differential roles in the generation of pacemaking activity, maintenance of the plateau, or release of calcium from intracellular pools. Recently, data have been presented that show the presence of two types of calcium channels in canine atrial myocytes (13). Single-channel data from isolated guinea pig ventricular myocytes also suggest the existence of two calcium channel types (14). In this communication, we provide further evidence for the presence of two types of calcium channels in single internally dialyzed guinea pig ventricular myocytes using only calcium (5-15 mM) as the charge carrier. Our data clearly show that the two calcium channel types can be distinguished based on their activation threshold, inactivation kinetics, response to clamping frequency, and pharmacological sensitivity to various inorganic and organic calcium-channel blockers. METHODSGuinea pig ventricular myocytes were isolated by using a newly developed collagenase-protease technique (15). Guinea pigs (body weight, 200-400 g) were heparinized (10 units/g) 10 min prior to anesthe...

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