Characterization of Cardiovascular Alterations Induced by Different Chronic Cisplatin Treatments

Abstract

In the last years, many clinical studies have revealed that some cisplatin-treated cancer survivors have a significantly increased risk of cardiovascular events, being cisplatin-induced cardiovascular toxicity an increasing concern. The aim of the present work was to evaluate the cardiovascular alterations induced by different chronic cisplatin treatments, and to identify some of the mechanisms involved. Direct blood pressure, basal cardiac (left ventricle and coronary arteries) and vascular (aortic and mesenteric) functions were evaluated in chronic (5 weeks) saline- or cisplatin-treated male Wistar rats. Three different doses of cisplatin were tested (1, 2, and 3 mg/kg/week). Alterations in cardiac and vascular tissues were also investigated by immunohistochemistry, Western Blot, and or quantitative RT-PCR analysis. Cisplatin treatment provoked a significant modification of arterial blood pressure, heart rate, and basal cardiac function at the maximum dose tested. However, vascular endothelial dysfunction occurred at lower doses. The expression of collagen fibers and conexin-43 were increased in cardiac tissue in cisplatin-treated rats with doses of 2 and 3 mg/kg/week. The expression of endothelial nitric oxide synthase was also modified in cardiac and vascular tissues after cisplatin treatment. In conclusion, chronic cisplatin treatment provokes cardiac and vascular toxicity in a dose-dependent manner. Besides, vascular endothelial dysfunction occurs at lower doses than cardiac and systemic cardiovascular toxicity. Moreover, some structural changes in cardiac and vascular tissues are also patent even before any systemic cardiovascular alterations.

Changes in the diet composition of fatty acids and fiber affect the lower gastrointestinal motility but have no impact on cardiovascular parameters: In vivo and in vitro studies

“…The experiment was performed according to the protocol established by Herradón et al Briefly, the aorta was excised and placed in ice‐cold Krebs‐Henseleit (K‐H) solution (118 NaCl; 4.75 KCl; 1.2 MgSO 4 ; 1.19 KH 2 PO 4 ; 2.54 CaCl 2 ; 25 NaHCO 3 ; 11 glucose). Transverse vascular rings 3‐4 mm long were fixed vertically and suspended in a 5‐mL jacketed glass organ bath containing K‐H buffer (95% O 2 , 5% CO 2 , 37°C).…”

“…To assess contractile function, phenylephrine (PE; 10 −9 M to 10 −5 M) concentration‐response curves were performed. To evaluate vascular endothelium‐dependent and endothelium‐independent relaxation, carbachol (10 −9 M to 10 −4 M) or sodium nitroprusside (SNP; 10 −9 M to 10 −6 M) concentration‐response curves, respectively, were established in PE (1 µM; submaximal) precontracted preparations . Only one concentration‐response curve was carried out in each preparation.…”

May a sigma‐1 antagonist improve neuropathic signs induced by cisplatin and vincristine in rats?

“…), a catheter coupled to a pressure transducer was inserted in the animals’ right carotid artery for direct measurement of systolic (SBP) and diastolic (DBP) arterial blood pressure and heart rate, using a PowerLab/4e recording system (PanLab S.L., Barcelona, Spain). Recording these cardiovascular parameters lasted for 10 min (Herradón et al., ). After blood pressure measurements, animals were euthanized, and the following preparations were conducted to perform the following experiments.…”

Copper Complexes as Anticancer Agents Targeting Topoisomerases I and II

“…Cisplatin and its derivative drugs (carboplatin of second generation and oxaliplatin of third generation) are used worldwide in clinical applications and several other platinum analogs (lobaplatin, nedaplatin, and heptaplatin) are approved in several countries ( Figure 1 ) [ 3 , 4 ]. However, serious side effects including toxicities on the kidney, heart, ear, and liver, decrease in immunity, hemorrhage, and gastrointestinal disorders limit the use of platinum derivatives [ 5 , 6 , 7 ]. The appearance of drug resistances, issuing from acquired or intrinsic multiple genetic and epigenetic changes, has also limited the clinical use of platinum-derived drugs [ 8 ].…”