Angiotensin II (Ang II) has various cardiac effects and causes vasoconstriction. Ang II activates the type-1 angiotensin receptor—Gq/11 signaling pathway resulting in the release of 2-arachidonoylglycerol (2-AG). We aimed to investigate whether cardiac Ang II effects are modulated by 2-AG-release and to identify the role of type-1 cannabinoid receptors (CB1R) in these effects. Expression of CB1R in rat cardiac tissue was confirmed by immunohistochemistry. To characterize short-term Ang II effects, increasing concentrations of Ang II (10−9–10−7 M); whereas to assess tachyphylaxis, repeated infusions of Ang II (10−7 M) were administered to isolated Langendorff-perfused rat hearts. Ang II infusions caused a decrease in coronary flow and ventricular inotropy, which was more pronounced during the first administration. CB agonist 2-AG and WIN55,212-2 administration to the perfusate enhanced coronary flow. The flow-reducing effect of Ang II was moderated in the presence of CB1R blocker O2050 and diacylglycerol-lipase inhibitor Orlistat. Our findings indicate that Ang II-induced cardiac effects are modulated by simultaneous CB1R-activation, most likely due to 2-AG-release during Ang II signalling. In this combined effect, the response to 2-AG via cardiac CB1R may counteract the positive inotropic effect of Ang II, which may decrease metabolic demand and augment Ang II-induced coronary vasoconstriction.
Sphingosine-1-phosphate (S1P) is a lysophospholipid mediator with diverse biological function mediated by S1P1–5 receptors. Whereas S1P was shown to protect the heart against ischemia/reperfusion (I/R) injury, other studies highlighted its vasoconstrictor effects. We aimed to separate the beneficial and potentially deleterious cardiac effects of S1P during I/R and identify the signaling pathways involved. Wild type (WT), S1P2-KO and S1P3-KO Langendorff-perfused murine hearts were exposed to intravascular S1P, I/R, or both. S1P induced a 45% decrease of coronary flow (CF) in WT-hearts. The presence of S1P-chaperon albumin did not modify this effect. CF reduction diminished in S1P3-KO but not in S1P2-KO hearts, indicating that in our model S1P3 mediates coronary vasoconstriction. In I/R experiments, S1P3 deficiency had no influence on postischemic CF but diminished functional recovery and increased infarct size, indicating a cardioprotective effect of S1P3. Preischemic S1P exposure resulted in a substantial reduction of postischemic CF and cardiac performance and increased the infarcted area. Although S1P3 deficiency increased postischemic CF, this failed to improve cardiac performance. These results indicate a dual role of S1P3 involving a direct protective action on the myocardium and a cardiosuppressive effect due to coronary vasoconstriction. In acute coronary syndrome when S1P may be released abundantly, intravascular and myocardial S1P production might have competing influences on myocardial function via activation of S1P3 receptors.
Telemonitoring systems equipped with photoplethysmography-based contour analysis of the digital arterial volume pulse (DVP) can be optimal tools for remote monitoring of cardiovascular patients; however, the method is known to be sensitive to errors. We aimed to show that DVP analysis is a reliable method to track cardiovascular status. We used our proprietary SCN4ALL telemedicine system and analyzed nine parameters derived from the DVP and its second derivative (SDDVP). First, we assessed the repeatability of system measurements by detecting artificial signals. Then test–retest reliability of human measurements was evaluated in healthy individuals under standardized conditions. The SCN4ALL system analyzed each parameter with high accuracy (coefficients of variation (CVs) < 1%). Test–retest reliability of most parameters (stiffness index, reflection index, left ventricular ejection time index, b/a, heart rate) was satisfactory (CVs < 10%) in healthy individuals. However, aging index and d/a ratio derived from the SDDVP were more variable. Photoplethysmography-based pulse contour analysis is a reliable method to monitor cardiovascular status if measurements are performed with a system of high accuracy. Our results highlighted that SDDVP parameters can be interpreted with limitations due to (patho)physiological variations of the DVP. We recommend the evaluation of these parameters only in measurements where all inflections of SDDVP are detected reliably.
Background Introduction of telemonitoring systems to patient care which provide extensive information about the cardiovascular status of the patient is a promising direction to reduce cardiovascular morbidity and mortality. Our team has developed a telemedical system which is based on the photoplethysmographic detection of the digital arterial pulse wave. The system incorporates a cloud-based automated algorithm which analyses the pulse contour to provide 15 scientifically established parameters for versatile characterization of cardiovascular function. The aim of the current study was to assess the variability of the measurements to test the applicability of the tool before clinical use. We assessed the repeatability of the measurements by detecting stable artificial signals, and also test-retest variability by repeatedly examining the pulse contours of healthy individuals under standardized conditions. Results Most contour parameters (stiffness index, reflection index, left ventricular ejection time index and mean interbeat intervals) are measured with high repeatability (coefficients of variation (CV) < 1% for each parameter), and exhibit acceptable intrapersonal fluctuations (CVs < 10%). However, some parameters derived from the second derivative of the pulse wave seem to be more variable (aging index, d/a ratio). This is explained by the typical alterations of the pulse wave under specific circumstances, which cause the flattening or complete disappearance of c and d inflections on the second derivative. Conclusion Our measurements proved that our telemonitoring system detects and analyses digital pulse contours with high accuracy and highlighted that second derivative parameters should be interpreted cautiously. We recommend the evaluation of these parameters only in those measurements where c and d points are detected reliably. Pulse contour parameters are stable in healthy individuals under standardized conditions, which allows detection of subtle abnormal alterations by the remote surveillance system.
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