Experience and improvement in establishing an abdominal working heart transplantation model in rats / 中国实验动物学报

Objective To modify the techniques for establishment of an abdominal working heart transplantation model in rats and to sum up the key factors to success.Methods A total of 180 12-week old Brown Norway rats ( donor) and Lewis rats ( recipient) were used in this study:50 BN rats and 50 Lewis rats for pilot experiment, and 40 BN rats and 50 Lewis rats for the formal experiment.The rat model of working heart heterotopic transplantation was adopted and estab-lished by Wiedemann’ s mode.We transplanted the heart from BN rats to Lewis rats and analyzed the survival rate, causes of death and histological changes of the heart ( HE staining) in this experiment.Results After exercise and modification, the survival rate was increased to 77.5%, and the mean total duration of operation was 71 ±11 min, and the mean ische-mic time of the donor hearts was 34 ±5 min.Histological examination ( HE staining) of the cardiac allograft showed a mild inflammatory cell infiltration in the graft at 24 h after transplantation, indicating that the model was reliable.Conclusions A variety of factors may affect the final operation success rate in the establishment of this heart transplantation model.A-mong them, the major affecting factors include: healthy animals, donor heart protection, rapid and effective vascular su-ture, and postoperative animal management.

Modulation of the respiratory rhythm by gap-junction blockers 18-α-glycyrrhetinic acid and 18-β-glycyrrhetinic acid.

Gap junction proteins are expressed in the pre-Bötzinger complex of the respiratory network but it remains under discussion how they modulate the respiratory rhythm generation. In the present study we tested whether the gap junction blockers 18-β-glycyrrhetinic acid (18-β- GA) and 18-α-glycyrrhetinic acid (18-α-GA) change either the phrenic nerve (PN) discharge frequency or amplitude. The PN discharge was recorded using the working heart-brainstem preparation of adult wistar rats (P22- P28) exposed to increasing concentrations of the gap junction blockers (0.1; 1; 10; 20 μM). With the two lower concentrations (0.1; 1 μM) of 18-β-GA, PN discharge frequency decreased to 46±15% (p=0.007) of the control value while it increased to 173±57% (p=0.16) with the two higher concentrations (10; 20 μM). Surprisingly, with 18-α-GA the PN discharge frequency was not significantly changed with any of the concentrations used. Enhancing the respiratory drive with 12% CO2, the PN discharge frequency increased tendencially with rising concentrations of 18-β-GA, but again no significant change was observed with 18-α-GA. PN-amplitudes were slightly reduced over the course of the experiments, while the frequency of the heartbeat was not significantly changed at any time with any concentration.

Effects of total flavones metasequosia on ischemia reperfusion injury in guinea pig working heart / 中国药理学通报

AIM To investigate the effects of t ot al flavones metasequosia (TFM) on ischemia reperfusion injury in guinea pig work ing heart. METHODS Ischemia reperfusion injury model was used to evaluate the effects of TFM. Myocardial func tion, the content of CK、LDH and the activity of MDA were measured. RESU LT TFM improved the cardiac function, decreased the release of LDH and CK and inhibited the increase of MDA content. CONCLUSION TFM had a protective effect on ischemia reperfusion injury of myocardium which could be re lated to its inhibitory effect on lipid peroxidation.

Influence of Bupivacaine on the Coronary Flow Rate of the Isolated Rat Heart / 대한마취과학회지

To darify the cardiotoxic mechanism, the effect of bupivacaine on the cardiac function, especially in coronary flow rate was inveetigated in the isolated working rat heart. When administered into left atrium of the heart, lidocaine(10(-6)-10(-4) M) decreased heart rate in a dose-related fashion, whereae rate of coronary flow and mean coronary resistance tend to decrease and increase transiently, respectively. On the other hand, bupivacaine decreased the coronary flow rate and increased the mean coronary resistanee in a dose(10(-6)-10(-4) M) dependent manner. However, the decrement of heart rate by bupivacaine was not clear, but larger dose(10(-4) M) produced marked bradycardic effect. Bupivaeaine decreased the coronary flow and increased the mean coronary resistance in the isolated working heart, in which the heart rate and aortic pressure were kept constantly by electrical stimulation(3-6 pps, 0.5 mS, 20 V). These effects of bupivacaine were not influenced by 1 uM prazosin and 2 uM atropine pretreatment. But the bupivacaine effeets were completely abolished by 100 mM KC1 pretreatment and were inhibited markedly by 10(-7) M diltiazem, a Ca2+ -antagonist, pretreatment. From these results, it is suggested that the bupivacaine-induced coronary flow decrease is elicited via direct coronary vasoconstriction. And this vasoconstriction is due to the increments of intracellular Ca2+ concentration.

Histological Changes in the Heart-Lung Preparation by the Autoperfusion

The experimental study for extracorporeal preservation of the autoperfused working heart-lung preparation was performed in 5 dogs. Their weights were between 14??6kg, average of 14.8kg. The preparations were observed from 6 to 8 hours under autoperfusion, average of 5.2 hours. Hemodynamic and hematologic variables were measured during preharvest and autoperfusion. The experimental results during the autoperfusion were as follow : The arterial blood pH revealed severe respiratory alkalosis due to very low PaCO2. PaO2, 130~150mmHg remained constant; Heart rates remained constant at 110/min and the mean aortic pressures were maintained at 75mmHg; Serum Na and Ca showed mild decrease and serum K, moderate increase; Hemoglobulin and white cell count decreased progressively. The lung showed grossly focal congestion and atelectasis following 3~4 hours of autoperfusion and both findings worsened progressively, and little abnormality appeared in the heart. According to the light microscopic findings in the lung, congestion increased 3~4hours following autoperfusion and worsened between the 6th and 8th hours of autoperfusion. Atelectasis, inflammatory infiltration, edema, and hemorrhage worsened after the 4th hour. Emphysematous changes were initially severe to decreasel later on. Hyaline membrane developed after 6 to 8 hours. Hyaline thrombi appeared after 2 hours. The heart was examined by and electron microscope. Vacuolization increased mildly at the 6th to 7th hour. Mitochondrial swelling and cellular swelling showed focally near the end of the perfusion. Glycogen amount was rich throughout the perfusion. It was concluded that the heart preservation was good but the preparation of the lung seemed to be inadequate after 3~4 hours by this autoperfusion technique.

Study on antioxidant effect of Astragalus polysaccharide / 中国药理学通报

Xanthine-Xanthine oxidase ( X-XOD) added to the culture medium of cultured cardiac cells in rats may damage cell membrane. Electrophysiological findings indicated that APA, MDP, OS,Vmax, were decreased and the SDF was increased. Astragalus polysaccharide (APS) could protect the cells from being damaged by X-XOD. APS recoverted all the de-creased cardiac functional parameters in free-radical-damaged rats by X-XOD. APS had anti-free-radical damage action on the cultured my-ocardiocytes and the myocardial contractility of the isolated rat working heart.

IMPROVEMENT ON ISOLATED GUINEA PIG WORKING HEART PREPARATION AND EFFECT OF COBRA CARDIOTOXIN / 中国药理学通报

Usually experiments done on isolated working heart preparation must be completed within 1 h, because of declining of cardiac functions after going beyond that limit reported by many authors. Our experiments on guinea pig showed that the viability time lasted at least 2 h. All measured indices of cardiac performance, namely LVP, dP/dtmax, MASP, HR, CF, AF, CO, LVPW, MVO2 and. working efficiency, remained stable within that period of time, .when PcO2 and PO2 of perfusing solution were adjusted at 4.7~7.3 kPa and over 67 kPa respectively, resulting in stability of pH value in 7.4 or so. Modification of the Krebs solution by devoid of phosphate and addition of pyruvate and EDTA may also be responsible for prolongation of the viability time. After such improvement, the preparation will give sufficient time to study the effect of drugs. Its use will be greatly widened.1 -10 mg/L cobra cardiotoxin increased CO, AF, LVEDP, MASP, LVP, dP/dtmax, decreased CF, and unchanged HR.MVO2 and working efficiency were insignificantly increased. These results obtained from this preparation were in accordance with that from other isolated cardiac preparations.

EFFECTS OF BERBAMINE HCL ON ISOLATED WORKING HEART OF GUINEA PIG / 中国药理学通报

The isolated working heart of guinea pig perfused with Tyrode's solution could work normally for at least 60 min. It was shown that berbamine ( BA ) could depress the function of isolated working heart of guinea pig in dose-dependent manner. BA 3 mol/L could decrease the left ventricular pressure, aortic pressure, -dP/dtmax, aortic blood flow and coronary blood flow, and increase left ventricular end-diastolic pressure. BA 100 mol/L could result in the ventricular asystole, however, no obvious influence the contraction of atrium.It was also demonstrated that BA could antagonise the arrhythmias induced by the adrenaline in isolated working heart of guinea Pig.