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OBJECTIVE To analyze the influential factors of cardioto xicity in patients with positive breast cancer of human epidermal growth factor receptor 2（HER-2）treated by trastuzumab combined with chemotherapy. METHODS From April 2017 to January 2021，200 HER-2 positive breast cancer patients receiving pirarubicin + cyclophosphamide combined with sequential paclitaxel+trastuzumab were collected from our hospital. According to the presence or absence of cardiotoxicity ，the patients were divided into cardiotoxicity group and non-cardiotoxicity group. The clinical data and echocardiographic results of the patients were collected，and the influential factors of cardiotoxicity were analyzed. RESULTS Among 200 patients，43 patients suffered from cardiotoxicity with the incidence of 21.5％. The proportion of patients with cardiotoxicity during pirarubicin+cyclophosphamide therapy accounted for 5.5％（11/200），and the proportion of patients with cardiotoxicity during sequential paclitaxel+trastuzumab therapy accounted for 20.5％（41/200）；the latter was significantly higher than the former （P＜0.01）. At the same time ，the decrease of left ventricular ejection fraction during sequential therapy of paclitaxel and trastuzumab was significantly higher than that during pirarubicin+cyclophosphamide therapy [ 14％（12％，17％）vs. 7％（3％，10％），P＜0.001]. Compared with patients without cardiotoxicity ，the proportion of patients with cardiotoxicity with a history of hyperlipidemia was significantly higher （P＜ 0.01），while the proportion of patients receiving dexrazoxane was significantly lower （P＜0.01）. Results of binary Logistic regression analysis showed that the history of hyperlipidemia [OR ＝3.672，95％ CI（1.499，8.992），P＝0.004] and the use of dextrazoxane [OR ＝0.154，95％ CI（0.072，0.330）， P＜0.001] were associated with the occurrence of cardiotoxicity. CONCLUSIONS Hyperlipidemia is an independent risk factor for cardiotoxicity induced by pirarubicin + cyclophosphamide combined with sequential paclitaxel+trastuzumab in HER 2 positive breast cancer patients ，while the use of dextrazoxane is a protective factor.
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Aim To study the mechanisms of inotropic responses to doxazosin enantiomers in the isolated rat atrium.Methods We analyzed the positive inotropic response to (-)doxazosin and the negative inotropic response to (+)doxazosin in the left atrium of rat u-sing receptor-pharmacological technique.Results In the preparation treated with verapamil,the positive in-otropic responses to 3 μmol·L-1 (-)doxazosin were significantly inhibited from the control level (245.7 1 ± 44.29)mg to (172.50 ±43.34)mg,(P<0.05).In the preparation treated with methylene blue,the posi-tive inotropic responses to 3 μmol·L-1 (-)doxazosin were significantly potentiated from the control level (245.7 1 ±44.29 )mg to (303.33 ±45 .90 )mg,(P<0.05 ).In the preparation treated with H-89 ,the positive inotropic responses to 3,10 and 30 μmol · L-1 (-)doxazosin were (338.57 ±96.86 ) mg, (471.43 ±107.61)mg and (520.00 ±103.44)mg, which were significantly (P<0.05 ~0.01)larger than the control levels of (245.71 ±44.29)mg,(314.29 ±90.34)mg and (357.14 ±68.49 )mg.Treatment with phenoxybenzamine,atropine,propranolol or indo-methacin did not significantly affect the responses to doxazosin enantiomers.Conclusion The positive ino-tropic responses to (-)doxazosin in the isolated left a-trium of rat are partially involved in L-type Ca2+chan-nels and intracellular cGMP level.However,α-adre-noceptors,muscarinic receptors,β-adrenoceptors and cyclooxygenases are not related to the responses to doxazosin enantiomers.
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Aim To analyze the blocking effect of ( ± ) doxazosin [ ( ± ) DOX ] , ( -) doxazosin [ ( -) DOX] and ( +) doxazosin [( +) DOX] on the vaso-constriction of rat isolated mesenteric arterioles media-ted by α1-adrenoceptors. Methods The vasoconstric-tion induced by phenylephrine ( Phe) in the rat isola-ted mesenteric arterioles ( the second- and third-order branches) was recorded using DMT wire myograph sys-tem 620M, and theα1-adrenoceptor antagonistic activ-ity of ( ± ) DOX and its enantiomers was analyzed. Results The inner diameter of second- and third-or-der branches of the rat mesenteric artery was (162. 5 ± 5. 3) μm (n=11) and (103. 1 ± 2. 3) μm (n=23), respectively. The values of normalized preload of the second-and third-order branches, which were calculat-ed by the LabChart software, were (2. 93 ± 0. 51) mN ( n =11 ) and ( 2. 64 ± 0. 50 ) mN ( n =23 ) ( P >0. 05 ) . Vasoconstrictive responses to Phe in the sec-ond-order branche of rat mesenteric artery under nor-malized preloads were not significantly different from those under 5 mN preload;however, the Emax values of the Phe-induced vasoconstriction under 10 mN, 15 mN and 20 mN preloads were decreased by 12%, 29%and 43% ( P<0. 01 ) respectively compared with those under normalized preload. The concentration-response curves for Phe were shifted to right in a concentration dependent manner by ( -) DOX or ( +) DOX at 0. 001 , 0. 01 and 0. 1 μmol · L-1 without significant change in their Emax values in the second-and third-or-der branches of rat mesenteric artery. Schild plot anal-ysis indicated that ( -) DOX, ( +) DOX and ( ± ) DOX non-competitively inhibited the vasoconstrictive responses to Phe in the second-order branches, and the rank order of pKB values was ( +) DOX ( 8. 67 ± 0. 10 ) , ( ± ) DOX ( 8. 53 ± 0. 090 ) , ( -) DOX (7. 85 ± 0. 09). However, schild plot analysis indica-ted that ( -) DOX and ( +) DOX competitively inhibi-ted the vasoconstrictive responses for Phe in the third-order branch, and the rank order of their pKB values was ( ± ) DOX ( 8. 68 ± 0. 17 ) , ( +) DOX ( 8. 48 ± 0. 10 ) , ( -) DOX ( 7. 48 ± 0. 140 ) . Conclusion The α1-adrenoceptor blocking activity of ( -) DOX is much weaker than that of ( +) DOX or ( ± ) DOX in the rat isolated mesenteric arterioles, and there is a tendency to enhance the activity of ( ± ) DOX in third-order branches of the rat mesenteric artery though theα1-adrenoceptor blockade effect of ( ± ) DOX is not significantly different from ( +) DOX.