The effects of adenocaine (adenosine and lidocaine) on early post-resuscitation cardiac and neurological dysfunction in a porcine model of cardiac arrest

Aim

Return of spontaneous circulation (ROSC) elicits ischaemia/reperfusion injury and myocardial dysfunction. The combination of adenosine and lidocaine (AL, adenocaine) has been shown to (1) inhibit neutrophil inflammatory activation and (2) improve left ventricular function after ischaemia. We hypothesized that resuscitation with adenocaine during early moments of cardiopulmonary resuscitation (CPR) attenuates leucocyte oxidant generation and myocardial dysfunction.

Methods

Pigs were randomized to: (1) sham (n = 7), (2) cardiac arrest (CA; n = 16), or 3) cardiac arrest + adenocaine (CA + AL; n = 12). After 7 min of electrically induced ventricular fibrillation, start of CPR was followed by infusion of saline (CA) or adenocaine (CA + AL) for 6 min. Haemodynamics, cardiodynamics (pressure–volume loops) and leucocyte superoxide anion generation were assessed. Neurological function was evaluated after 24 h by histology and neurological deficit score (0 = normal; 500 = brain dead).

Results

Rate of ROSC was comparable between groups: CA group 11/16 and CA + AL group 7/12 p = 0.57). Cardiac index transiently increased after ROSC in both groups. Left ventricular dysfunction demonstrated by a rightward shift of the intercept of end-systolic pressure–volume relations in CA was avoided in the CA + AL group. Leucocyte superoxide anion generation 2 h after ROSC was significantly attenuated in the CA + AL group compared to the CA group. Neurological deficit scores [CA: median: 17.5(IQR:0–75) and CA + AL: 35(IQR:15–150)] and histopathological damage were comparable in both groups (p = 0.37).

Conclusion

Infusion of adenocaine during early resuscitation from CA significantly improved early post-resuscitation cardiac function and attenuated leucocyte superoxide anion generation, without a change in post-ROSC neurological function. (IACUC protocol number 023-2009).     

一种新的猪胰肾联合移植术式的实验研究

目的 :建立一种新的胰液肠引流式小型猪胰肾整块联合移植模型 ,探讨胰肾联合移植 (SPKT)的最佳术式及早期并发症。方法 :7头供体猪分别进行胰、脾、部分十二指肠、肾、输尿管多器官联合整块切取 ,将其脾动、静脉分别与左肾动、静脉行端端吻合 ,切除右肾及脾。将移植物的腹主动脉、门静脉与 7头受体猪腹主动脉、下腔静脉行端侧吻合 ,供体十二指肠侧壁与受体上段空肠行侧侧吻合 ,输尿管置管外引流。结果 :7头受体顺利完成胰肾联合移植术 ,术后移植物平均存活 ( 3 9± 1 2 )d ,存活期胰肾功能基本正常。本动物模型未发现胰液肠引流术式常见的早期并发症。结论 :猪胰液肠引流式胰肾整块联合移植模型建立成功。该术式受体创伤小 ,改良的肠胰液外分泌引流简单有效。     

Binding of muscarine receptor antagonists to pig coronary smooth muscle

Summary In order to characterize the muscarinic binding site on coronary smooth muscle, we investigated the binding properties of (³H)quinuclidinyl benzilate (QNB) in membrane preparations of pig coronary arteries and atria. Scatchard analysis and Hill plot showed that (³H)QNB binds to a single population of sites in both tissues. The binding profiles of the muscarine receptor antagonists atropine, 11-((2-((dimethylamino)methyl)-1-piperidinyl)acetyl)-5,11-dihydro-6H-pyrido(2,3-b) (1,4)benzodiazepine-6-one (AF-DX 116), pirenzepine, and 4-diphenylacetoxy-Nmethylpiperidine methiobromide (4-DAMP) in both tissues were compared with binding data from other tissues, representative for different muscarinic binding site subtypes. It is concluded that the pig coronary smooth muscle muscarinic binding site is different from M₁ and M₂ binding sites investigated so far. Send offprint requests to I. Rinner     

5-Hydroxytryptamine-induced increase in left ventricular dP/dtmax does not suggest the presence of ventricular 5-HT4 receptors in the pig

Summary Although 5-hydroxytryptamine (5-HT) increases porcine atrial force and rate via 5-HT₄ receptors, its effect on left ventricular contractility is not known. Therefore, using the maximum rate of rise of left ventricular pressure (LVdP/dt_max) as an index of cardiac contractility, we have attempted to analyze the possible role of ventricular 5-HT₄ receptors in the anaesthetized pig. The full agonists at 5-HT₄ receptors, 5-HT and 5-methoxytryptamine (each 3, 10 and 30 g · kg^–1), and the -adrenoceptor agonist, isoprenaline (0.01, 0.03 and 0.1 g · kg^–1), increased heart rate, LVdP/dt_max and cardiac output. For a given degree of tachycardia, the increase in LVdP/dt_max by isoprenaline was substantially more than that observed with either 5-HT or 5-methoxytryptamine. The 5-HT₄ receptor partial agonist, renzapride (3, 10, 30, 100 and 300 g · kg^–1), also increased heart rate and LVdP/dt_max dose-dependently. When the heart was paced at 150 beats · min^–1, increases in LVdP/dt_max as well as cardiac output (except with the highest doses) by 5-HT, 5-methoxytryptamine and isoprenaline were clearly attenuated. However, the magnitude of attenuation of LVdP/dt_max responses by cardiac pacing was more marked in the case of 5-HT and 5-methoxytryptamine than with isoprenaline.The effects of renzapride (300 g · kg^–1) and tropisetron (0.3 and 3 mg · kg^–1) on increases in heart rate and LVdP/dt_max by 5-HT, 5-methoxytryptamine and isoprenaline were also studied. In the absence of atrial pacing, both renzapride and tropisetron (3 mg · kg^–1) effectively antagonized the responses to 5-HT and 5-methoxytryptamine; except for some decrease in the LVdP/dt_max response by tropisetron, the effect of isoprenaline remained essentially unchanged after the antagonists. During atrial pacing, renzapride significantly antagonized the responses to the first two doses of 5-HT, but the responses to the highest 5-HT dose and to 5-methoxytryptamine remained unaffected. Though, particularly after its higher dose, tropisetron reduced the responses to 5-HT and 5-methoxytryptamine, isoprenaline responses were also affected.The above results show that a significant part of the increase in LVdP/dt_max by 5-HT receptor agonists in the anaesthetized pig is a consequence of tachycardia elicited by these compounds via 5-HT₄ receptors. Since the increase in LVdP/dt_max, compared to tachycardia, was much less with 5-HT and 5-methoxytryptamine than with isoprenaline, and since the antagonism by renzapride and tropisetron against 5-HT and 5-methoxytryptamine during atrial pacing was relatively weaker and/or unspecific, it appears unlikely that the increase in LVdP/dt_max, during atria] pacing is mediated by ventricular 5-HT₄ receptors. This view is substantiated by our recent in vitro experiments where 5-HT (0.01 to 100 mol/l) failed to significantly increase contractions of porcine left ventricular trabeculae.Correspondence to P. R. Saxena at the above address     

猪肾中砷的氢化物发生原子荧光测定法

目的研究氢化物发生—原子荧光法测定猪肾中砷的适宜条件。方法试验酸介质和还原剂用量对测定砷的影响;选择仪器的最佳工作条件及氢化物发生条件;试验样品中常见元素对砷测定的干扰情况及消除方法。结果在测定条件下,砷的线性范围为0~200μg/L,相关系数达0.999 3以上;检出限为0.14μg/L,回收率在95.5%~101.0%之间,相对标准差(n=7)小于2.7%。结论该试验选用5.0%HCl为介质;样品测定原子化观察高度8 mm;5%硫脲 5%抗坏血酸混合溶液掩弊干扰效果最好。在该工作条件下测定猪肾中的砷,方法灵敏度高,准确度、精密度好。     

猪心肌梗死模型的建立

目的：建立能长期存活的猪实验性心肌梗死模型。方法：11头8-12个月、体重30-40kg的成年版纳微型猪,采用氯胺酮加安定和芬太尼作混合静脉麻醉,开胸暴露心脏后结扎左冠状动脉前降支距终末端1/3稍高处,4周后取出心脏标本。结果：11头猪中有6头手术成功,4周后的心脏标本显示心肌梗死面积占左心室面积的5.73%-15.40%,平均11.61%。有5头猪因结扎部位较高（在左冠状动脉前降支中段）而于手术中发生心室扑动或心室纤颤死亡。结论：成功建立了猪实验性心肌梗死模型,方法简便易行,猪能长期存活。     

The toxic mechanism and metabolic effects of atractyloside in precision-cut pig kidney and liver slices

The toxic and cellular metabolic effects of atractyloside, a diterpenoid glycoside, which causes fatal renal and hepatic necrosis in vivo in animals and humans, have been investigated in tissue slices prepared from male domestic pig kidney and liver. Precision-cut slices (200 μm thick) were incubated with atractyloside at concentrations of 200 μM, 500 μ M, 1.0 mM and 2.0 mM for 3 h at 37 °C and changes in lipid profile and pyruvate-stimulated gluconeogenesis investigated. Lipid peroxidative changes, reduced glutathione (GSH) and ATP content, the release of lactate dehydrogenase (LDH), alkaline phosphatase (ALP), alanine and aspartate aminotransferase (ALT/AST) were also assessed. After 3 h of incubation, atractyloside caused a significant (P < 0.01) and concentration-dependent leakage of LDH and ALP from kidney slices. Only LDH leakage was significantly elevated in liver slices while ALT and AST leakage showed marginal increase. Atractyloside at concentrations of ≥200 μ M caused a significant increase in lipid peroxidation, but only in liver slices. However, atractyloside at concentrations of ≥200 μ M caused a marked depletion of GSH and ATP content in both kidney and liver slices. There was a marked decrease in total and individual phospholipid in kidney but not in liver slices. However, cholesterol and triacylglycerol levels were not affected by atractyloside in both kidney and liver slices. Renal and hepatic pyruvate-stimulated gluconeogenesis were significantly (P < 0.05) inhibited at atractyloside concentrations of ≥500 μM. Accumulation of organic anion p-aminohippuric acid (PAH) was also inhibited in renal cortical slices at atractyloside concentrations of ≥500 μM. These results suggest that the observable in vivo effect of atractyloside can be reproduced in slices and that basic mechanistic differences exist in the mode of toxicity in liver and kidney tissues. The data also raise the possibility that the mechanistic basis of metabolic alterations in these tissues following treatment with atractyloside may be relevant to target selective toxicity. Received: 21 January 1998 / Accepted: 23 March 1998     

Postnatal growth of lung parenchyma in the piglet: Morphometry correlated with mechanics

Background: A previous study of piglet lung growth (Mansell et. al. 1989. J. Appl. Physiol., 67:1422–1427) showed transient stiffness to changes in shape and volume immediately after birth. Later, elastic recoil was found to increase as the lung grew in weight and volume. The present study uses morphometry to test possible structural correlates of these two mechanical changes. Methods: Piglet lungs were fixed near full inflation via the airways during the immediate newborn period (6–12 hours, n=3), at 3–5 days (n=6), 25–30 days (n=5), and 80–85 days (n=3). Morphometry comprised arithmetic and harmonic mean thicknesses of alveolar septae and average mean surface curvature. Measurements of curvature and airspace volume were combined to differentiate alveolar expansion from septal proliferation as mechanisms for volumetric growth. Results: The unique mechanical behavior of the newborn lungs was associated with relatively thick alveolar septae. Marked thinning of the septae and resolution of the stiffness to shape and volume change had occurred by 3–5 days. An increase in elastic recoil during the first postnatal month was found to be associated with simple airspace expansion. The second and third months were characterized by septal proliferation and increase in arithmetic mean septal thickness but elastic recoil did not increase further. Harmonic mean septal thickness and airspace volume per gram of lung tissue did not change over the course of the study. Conclusions: 1) A relative stiffness to shape and volume change in freshly newborn piglet lung is associated with relatively thick alveolar septal walls; 2) postnatal development of piglet lung parenchyma involves septal lengthening and thinning followed by septal proliferation; 3) the initial phase of septal lengthening, rather than the later phase of septal proliferation, is associated with increase in parenchymal recoil. © 1995 Wiley-Liss, Inc.