Clinical cardiac electrophysiologic evaluation of the positive inotropic agent, DPI 201-106

DPI 201-106 is a new positive inotropic agent. The cardiac electrophysiology of 16 patients was studied before and during DPI 201-106 administration (loading dose of intravenous DPI 201-106, 1·8 mg kg−1 h−1 administered over 10 min, followed by a maintenance dose of 0·2 mg kg−1 h−1). DPI 201-106 had no effect on the sinus node. The AH interval during fixed-rate atrial pacing became prolonged during DPI 201-106 infusion. There was a significant prolongation of the QT interval [QT (corrected), 417 ± 22 to 502 ± 35 ms, P<0·05; QT (atrial pacing at 600 ms), 374 ±17 to 419 ± 23 ms, P<0·05; QT (ventricular pacing at 600 ms), 409 ± 37 to 449 ± 30 ms, P<0·05]. The ventricular effective refractory period significantly prolonged during DPI 201-106 administration (242 ± 21 to 287 ± 56 ms, P < 0·05), but the supernormal-period duration decreased. The atrial effective refractory period was shortened in four patients and prolonged in one (261 ± 67 to 240 ± 53 ms, NS). The corrected atrial repolarization time (PTac) shortened significantly during DPI 210-106 infusion (479 ± 26 to 445 ± 22 ms at 20 min of the maintenance dose, P<0·05). Atrial fibrillation was initiated in five patients during DPI infusion, but no ventricular arrhythmia was provoked. These findings suggest that DPI 201-106 has novel differential electrophysiological effects on atria and ventricle

Cardiopulmonary disease as sequelae of long-term COVID-19: Current perspectives and challenges

COVID-19 infection primarily targets the lungs, which in severe cases progresses to cytokine storm, acute respiratory distress syndrome, multiorgan dysfunction, and shock. Survivors are now presenting evidence of cardiopulmonary sequelae such as persistent right ventricular dysfunction, chronic thrombosis, lung fibrosis, and pulmonary hypertension. This review will summarize the current knowledge on long-term cardiopulmonary sequelae of COVID-19 and provide a framework for approaching the diagnosis and management of these entities. We will also identify research priorities to address areas of uncertainty and improve the quality of care provided to these patients

Non-invasive assessment of early cardiac involvement in systemic sclerosis.

Twenty-eight patients with wide spectrum organ involvement of progressive systemic sclerosis but without signs or symptoms suggestive of cardiac involvement were studied by non-invasive cardiac techniques. The 12-lead electrocardiogram showed abnormalities in 6 patients: one had abnormal T waves and 5 had complete or incomplete right bundle branch block. Twenty-four hour ambulatory electrocardiography demonstrated higher average heart rates than in similar aged controls (82 +/- 9 vs 74 +/- 9 beats/min, P less than 0.05). In one patient a short run of ventricular tachycardia was recorded. No other significant arrhythmia was documented. Echocardiographic measurements were within normal ranges but small pericardial effusions were observed in two patients (7%). Resting first pass radionuclide angiography, utilizing 12 mCi of technetium 99m were performed in 23 patients. Seven patients (30%) had abnormal wall motion (diffuse hypokinesia), with a significant decrease in ejection fraction in comparison to those with normal wall motion (44 +/- 6% vs 60 +/- 6% P less than 0.01). Those with abnormal wall motion had suffered the disease longer than those with normal wall motion (13 +/- 4 vs 9.5 +/- 7 y). In conclusion, the heart is involved in half of the patients in this series; non-invasive cardiac assessment is useful in disclosing the early cardiac involvement and may influence long-term management

HIV and Schistosoma Co-Exposure Leads to Exacerbated Pulmonary Endothelial Remodeling and Dysfunction Associated with Altered Cytokine Landscape

HIV and Schistosoma infections have been individually associated with pulmonary vascular disease. Co-infection with these pathogens is very common in tropical areas, with an estimate of six million people co-infected worldwide. However, the effects of HIV and Schistosoma co-exposure on the pulmonary vasculature and its impact on the development of pulmonary vascular disease are largely unknown. Here, we have approached these questions by using a non-infectious animal model based on lung embolization of Schistosoma mansoni eggs in HIV-1 transgenic (HIV) mice. Schistosome-exposed HIV mice but not wild-type (Wt) counterparts showed augmented pulmonary arterial pressure associated with markedly suppressed endothelial-dependent vasodilation, increased endothelial remodeling and vessel obliterations, formation of plexiform-like lesions and a higher degree of perivascular fibrosis. In contrast, medial wall muscularization was similarly increased in both types of mice. Moreover, HIV mice displayed an impaired immune response to parasite eggs in the lung, as suggested by decreased pulmonary leukocyte infiltration, small-sized granulomas, and augmented residual egg burden. Notably, vascular changes in co-exposed mice were associated with increased expression of proinflammatory and profibrotic cytokines, including IFN-gamma and IL-17A in CD4(+) and gamma delta T cells and IL-13 in myeloid cells. Collectively, our study shows for the first time that combined pulmonary persistence of HIV proteins and Schistosoma eggs, as it may occur in co-infected people, alters the cytokine landscape and targets the vascular endothelium for aggravated pulmonary vascular pathology. Furthermore, it provides an experimental model for the understanding of pulmonary vascular disease associated with HIV and Schistosoma co-morbidity

Potential long-term effects of SARS-CoV-2 infection on the pulmonary vasculature: a global perspective.

The lungs are the primary target of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, with severe hypoxia being the cause of death in the most critical cases. Coronavirus disease 2019 (COVID-19) is extremely heterogeneous in terms of severity, clinical phenotype and, importantly, global distribution. Although the majority of affected patients recover from the acute infection, many continue to suffer from late sequelae affecting various organs, including the lungs. The role of the pulmonary vascular system during the acute and chronic stages of COVID-19 has not been adequately studied. A thorough understanding of the origins and dynamic behaviour of the SARS-CoV-2 virus and the potential causes of heterogeneity in COVID-19 is essential for anticipating and treating the disease, in both the acute and the chronic stages, including the development of chronic pulmonary hypertension. Both COVID-19 and chronic pulmonary hypertension have assumed global dimensions, with potential complex interactions. In this Review, we present an update on the origins and behaviour of the SARS-CoV-2 virus and discuss the potential causes of the heterogeneity of COVID-19. In addition, we summarize the pathobiology of COVID-19, with an emphasis on the role of the pulmonary vasculature, both in the acute stage and in terms of the potential for developing chronic pulmonary hypertension. We hope that the information presented in this Review will help in the development of strategies for the prevention and treatment of the continuing COVID-19 pandemic