Ultrastructure changes associated with brain death in the human donor heart

Electromicroscopic examinations were carried out on 30 myocardial biopsies taken from 22 human donor hearts immediately after excision (prestorage) or immediately before transplantation (post-storage). All electron micrographs were independently examined by two morphologists. Eleven structures were examined in each micrograph, and each structure was scored according to the degree of injury. A good interobserver correlation was obtained in 84 % of the structures scored. In the prestorage left ventricular biopsies (n = 11), approximately 20 %–25 % showed moderate to severe ultrastructural injury. The ultrastructural injury observed in the poststorage left ventricular biopsies (n = 15) was no different from that in the prestorage group, particularly injury to the sarcomere and mitochondria. A similar degree and pattern of injury was seen in the right ventricle (n = 4). There was no evidence that an ischemic storage period of less than 6 h increased the degree of injury seen. However, there was a higher incidence of moderate to severe injury in those hearts excised from donors initially dependent on high inotropic support.     

Leukocyte-depleted reperfusion of transplanted human hearts prevents ultrastructural evidence of reperfusion injury.

The present study examines whether leukocyte depletion can prevent postreperfusion ultrastructural injury in transplanted human hearts. Thirty-two patients undergoing orthotopic cardiac transplantation were randomized to receive either enriched, warm, whole blood (Group I; n = 16) or enriched, warm, leukocyte-depleted blood (Group II; n = 16) reperfusion. Donor hearts were arrested with 1 liter of 4 degrees C crystalloid cardioplegia and topically cooled. RV endomyocardial biopsies taken at end-ischemia and following reperfusion were assessed in a blinded fashion and graded according to injury (1 = minimal to 4 = severe). The mean ischemic time (Group I = 142 min, Group II = 153 min) was similar in the two groups. End-ischemic biopsies showed mild-moderate interstitial edema and mild capillary endothelial swelling in both groups with similar injury scores (Group 1 = 1.3 +/- 0.09 (means +/- SEM), Group 2 = 1.25 +/- 0.08). Postreperfusion biopsies in Group I showed nuclear chromatin clumping, moderate mitochondrial swelling, marked capillary endothelial swelling, and marked interstitial edema with a grade of 2.6 +/- 0.14 (P less than 0.001, paired t test). In contrast, postreperfusion biopsies in Group II showed minimal changes with a grade of 1.33 +/- 0.09, P less than 0.0001 in comparison to Group I Leukocyte-depleted reperfusion of human transplanted hearts prevents ultrastructural injury. This may allow safe extension of the ischemic period and result in improved graft function.     

Ultrastructural and cytochemical correlates of myocardial protection by cardiac hypothermia in man

We report observations on ultrastructural and cytochemical changes in the myocardium after hypothermic protection in 21 patients who underwent cardiac operation. Two general categories of hypothermic protection were studied. (1) topical cooling during anoxic arrest and moderate general hypothermia (10 patients with aortic valve replacement, Group 1) and (2) intermittent perfusion during moderate general hypothermia combined with topical cooling (11 patients with multiple valve replacement, Group II). Transmural left ventricular biopsies were taken at the start of the cardiopulmonary bypass and shortly after the end of aortic cross-clamping. In Group I (cross-clamp time, 51 +/- 12 minutes) only minor pathologic changes of the myocardial fine structure were found, with no differences among the left ventricular layers. In most mitochondria, structure remained intact but the mitochondrial granules disappeared. Cytochrome-c-oxidase activity was unchanged. In Group II (total cross-clamp time, 83 +/- 16 minutes) the subendocardium was well preserved. Slight subcellular damage comparable with that of resulting from topical cooling was seen in all hearts even after a total cross-clamp period of 106 minutes. Cytochrome-c-oxidase activity was unchanged. In the subepicardium, however, a positive correlation was found between the severity of ultrastructural damage and total cross-clamp time (p less than 0.05). Matrix clearing, damage to the cristae and the mitochondrial membranes, and nuclear abnormalities occurred when the aorta was cross-clamped for morethan 60 minutes. Cytochrome-c-oxidase activities decreased in these samples. It is concluded that: (1) no significant subcellular injury was found in hearts cooled topically during 1 hour of anoxic arrest; and (2) in hearts protected by intermittent perfusion during moderate general hypothermia and additional external cooling, the subendocardium was well preserved for anoxic periods of up to 106 minutes. However, after 60 minutes of aortic cross-clamping subcellular damage increased progressively in the subepicardium.     

Endotheliitis in chronic viral hepatitis: a comparison with acute cellular rejection and non-alcoholic steatohepatitis

Endotheliitis is an important histologic feature of acute cellular rejection (ACR) in the liver allograft. This change is not specific, however, and has been suggested to be associated with various liver diseases. End-stage liver disease owing to chronic hepatitis C is the leading indication for transplantation in North America, and its recurrence in allograft recipients is common. Because the presence of endotheliitis remains a diagnostic and therapeutic dilemma in transplant pathology, we investigated the prevalence and severity of endotheliitis in chronic liver diseases including hepatitis C. Endotheliitis was evaluated in 128 nontransplant liver biopsies of chronic liver diseases before therapy, including hepatitis C (HCV, n=62), hepatitis B (HBV, n=17), and nonalcoholic steatohepatitis (NASH, n=49). Eighty posttransplant biopsies with ACR were also reviewed. Subendothelial and supraendothelial endotheliitis were separately scored in the portal and central regions using a semiquantitative scoring system from 0 to 4. Pathologists were blinded to the clinical histories, and each biopsy was independently scored by 2 pathologists. Histologic activity index was also scored subsequently for cases of chronic HCV and HBV, using the modified Knodell (Ishak) score. Mean endotheliitis scores>1 were seen in 60%, 35%, and 6% of HCV, HBV, and NASH patients, respectively. The scores for portal subendotheliitis and supraendotheliitis were significantly higher in the viral hepatitis group than in the NASH group (P<0.01). There was no significant difference in the scores of endotheliitis comparing HCV to HBV. ACR group showed significantly higher scores in both portal and central subendotheliitis than any other group (P<0.00005). In the HBV and HCV groups with mean scores of portal subendotheliitis>1 (n=44), mean Ishak scores for portal inflammation and periportal injury were 2.43 and 2.34, respectively; whereas in those with less severe portal subendotheliitis (相似文献   

Myocardial and coronary effects of propofol in rabbits with compensated cardiac hypertrophy

BACKGROUND: Myocardial effects of propofol have been previously investigated but most studies have been performed in healthy hearts. This study compared the cardiac effects of propofol on isolated normal and hypertrophic rabbits hearts. METHODS: The effects of propofol (10-1,000 microM) on myocardial contractility, relaxation, coronary flow and oxygen consumption were investigated in hearts from rabbits with pressure overload-induced left ventricular hypertrophy (LVH group, n = 20) after aortic abdominal banding and from sham-operated control rabbits (SHAM group, n = 10), using an isolated and erythrocyte-perfused heart model. In addition, to assess the myocardial and coronary effects of propofol in more severe LVH, hearts with a degree of hypertrophy greater than 140% were selected (severe LVH group, n = 7). RESULTS: The cardiac hypertrophy model induced significant left ventricular hypertrophy (136+/-21%, P < 0.05). The pressure-volume relation showed normal systolic function but an altered diastolic compliance in hypertrophic hearts. Propofol only decreased myocardial contractility and relaxation at supratherapeutic concentrations (> or = 300 microM) in SHAM and LVH groups. The decrease in myocardial performances was not significantly different in SHAM and LVH groups. Propofol induced a significant increase in coronary blood flow which was not significantly different between groups. In severe LVH group, the degree of hypertrophy reached to 157+/-23%. Similarly, the effects of concentrations of propofol were not significantly different from the SHAM group. CONCLUSIONS: Propofol only decreased myocardial function at supratherapeutic concentrations. The myocardial and coronary effects of propofol were not significantly modified in cardiac hypertrophy.     

Myocardial and Coronary Effects of Propofol in Rabbits with Compensated Cardiac Hypertrophy

Background: Myocardial effects of propofol have been previously investigated but most studies have been performed in healthy hearts. This study compared the cardiac effects of propofol on isolated normal and hypertrophic rabbits hearts.

Methods: The effects of propofol (10-1,000 [mu]m) on myocardial contractility, relaxation, coronary flow and oxygen consumption were investigated in hearts from rabbits with pressure overload-induced left ventricular hypertrophy (LVH group, n = 20) after aortic abdominal banding and from sham-operated control rabbits (SHAM group, n = 10), using an isolated and erythrocyte-perfused heart model. In addition, to assess the myocardial and coronary effects of propofol in more severe LVH, hearts with a degree of hypertrophy greater than 140% were selected (severe LVH group, n = 7).

Results: The cardiac hypertrophy model induced significant left ventricular hypertrophy (136 +/- 21%, P < 0.05). The pressure-volume relation showed normal systolic function but an altered diastolic compliance in hypertrophic hearts. Propofol only decreased myocardial contractility and relaxation at supratherapeutic concentrations (>= 300 [mu]m) in SHAM and LVH groups. The decrease in myocardial performances was not significantly different in SHAM and LVH groups. Propofol induced a significant increase in coronary blood flow which was not significantly different between groups. In severe LVH group, the degree of hypertrophy reached to 157 +/- 23%. Similarly, the effects of concentrations of propofol were not significantly different from the SHAM group.     

Myocardial protective effect and its mechanism of leukocyte-depleted reperfusion in neonatal rabbit hearts

Thirty-six isolated blood-perfused hearts from newborn rabbits (age range, birth to 2 days) were subjected to 2 hours of cold global ischemia (15 °C), with an initial infusion of cold crystalloid cardioplegic solution, followed by 30 minutes of reperfusion (37 °C). The hearts were divided into two groups: those reperfused with whole blood (n = 18) and those reperfused with leukocyte -depleted blood (n = 18) obtained by the passage of blood through a leukocyte removal filter. At 30 minutes of reperfusion, the group of hearts reperfused with leukocyte-depleted blood showed significantly higher percentages of recovery in terms of the left ventricular developed pressure, the maximum rate of increase of left ventricular pressure, the rate pressure product, coronary sinus flow, and the adenosine triphosphate content in myocardium than did the group of hearts reperfused with whole blood. The hearts reperfused with leukocyte -depleted blood also showed significantly lower levels of malondialdehyde, chemiluminescence in the coronary sinus effluent, and counts of intracapillary neutrophils in myocardium than did the group of hearts reperfused with whole blood. The ultrastructural semiquantitative assessment in the myocardium showed that the mitochondrial and endothelial cell damages after 30 minutes of reperfusion were significantly less in the hearts reperfused with leukocyte-depleted blood than those in the hearts reperfused with whole blood. These results suggest that reperfusion with leukocyte-depleted blood prevents reperfusion injury in neonatal hearts, with possible attenuation of endothelial cellular injury and a subsequent no-reflow phenomenon.     

Effects of synthetic blood and crystalloid cardioplegic solutions on coronary endothelium: An experimental scanning electron microscope study

In an experimental study the effects of Fluosol DA (added with potassium chloride) on the vascular interface and endothelial cells were compared to those of crystalloid potassium cardioplegic solution using scanning electron microscope. Twenty rabbits (10 in each group) were sacrificed, the hearts with ascending aorta were immediately excised, and cold oxygenated solution was infused via a cannula inserted into the cross-clamped aorta. The hearts were left immersed in the perfusion medium for 2 hr. In the Fluosol DA group endothelial cover and endothelial cells were normal or minimal changes were seen in seven cases. Occasional breaking of intercellular attachments, small areas of denuded flow surface, and disappearance of microvilli were seen in three cases. In the crystalloid potassium cardioplegic group 7 of the 10 cases showed moderate or severe damage with large areas of denuded flow surface. The present experimental protocol represented an extreme situation where no collateral coronary blood was present. The coronary endothelial damage was obvious after the crystalloid potassium cardioplegic solution. Similar damage was not found following Fluosol DA infusion.     

The effect of hypothermic ischemia on recovery of left ventricular function and preload reserve in the neonatal heart

Neonatal and adult myocardium respond differently to ischemia. In addition, the neonatal heart possesses a limited preload reserve. The effect of uninterrupted hypothermic ischemia on recovery of left ventricular function and preload reserve was studied in two groups of isolated rabbit hearts: group 1 (neonates, n = 8), 7 to 10 days old; group 2 (adults, n = 15), 6 to 12 months old. Peak left ventricular systolic pressure, the first derivative of left ventricular systolic pressure, and heart rate were measured at left ventricular pressures of 0, 5, 10, and 15 mm Hg before and after 120 minutes of global ischemia at 27 degrees C. Before ischemia, left ventricular systolic pressure increased significantly at each increment of left ventricular end-diastolic pressure for both groups of hearts. After hypothermic ischemia, recovery of left ventricular systolic pressure was significantly reduced at each level of left ventricular end-diastolic pressure among neonatal hearts (range 75% to 79% of control values). The postischemic recovery of left ventricular systolic pressure in the adult hearts was markedly reduced from baseline values (range 43% to 53% of control values) and was significantly worse than that of neonatal hearts at each level of left ventricular end-diastolic pressure (p less than 0.001). Both groups were able to respond to increasing preload after ischemia. The slope of the curve describing the relationship between left ventricular end-diastolic pressure and percent recovery of left ventricular systolic pressure was not different from zero for neonatal hearts but was significantly greater than zero among the adults (0.22 +/- 0.21 versus 0.73 +/- 0.07, p = 0.0056). After ischemia, the first derivative of left ventricular systolic pressure fell significantly from control values among neonatal hearts (71% of control values). The reduction was considerably greater, however, among the adult hearts (54% of control values). These data indicate that the neonatal heart recovers systolic function better than the adult heart after global ischemia with moderate hypothermia.     

Enhanced myocardial protection with verapamil prior to postischemic reflow

Reperfusion of the heart after induced myocardial ischemia may be associated with severe myocardial damage, characterized by massive calcium influx and accumulation in the heart cells. The present study was undertaken to investigate whether verapamil, a slow channel calcium blocker, administered prior to reperfusion, might reduce this reflow injury without causing depression of heart function. Thirty-two isolated, perfused rabbit hearts were subjected either to 45 minutes of normothermic or 150 minutes of hypothermic global ischemia. Half of the heart in each group received verapaMil immediately prior to reperfusion, while the remaining hearts received no verapamil. Following ischemia and 60 minutes of reperfusion, left ventricular (LV) contractivity was superior in both groups of verapamil-treated hearts, compared to control hearts (LV developed pressure [DP] in normothermic hearts 63 +/- 6% of preischemic DP for verapamil-treated hearts versus 46 +/- 6% of preischemic DP for control hearts; in the hypothermic group, 65 +/- 8% of preischemic DP for verapamil-treated hearts versus 33 +/- 10% DP for control hearts). Postischemic LV compliance also was significantly improved in the verapamil-treated hearts through the period of reperfusion, compared to control hearts. No differences were noted in coronary flow, myocardial water content, or the onset of electromechanical activity between the verapamil and control hearts, but there was significantly improved ultrastructural preservation in both verapamil groups. These data demonstrate that verapamil, when administered just prior to reperfusion, results in improved recovery of myocardial function and excellent cellular preservation, presumably for reducing calcium influx into myocardial cells.     

不同程度呼吸机相关性肺损伤大鼠血清CC10蛋白水平的比较

目的 比较不同程度呼吸机相关性肺损伤(VILI)大鼠血清CCIO蛋白的水平.方法 清洁级Wistar大鼠40只,雌雄不拘,体重200～250 g,随机分为5组(n=8),对照组(Ⅰ组)仅切开气管,不行机械通气;轻度肺损伤组(Ⅱ组)潮气量(VT)7 ml/kg,机械通气2 h;中度肺损伤组(Ⅲ组)VT 7 ml/kg,机械通气4 h;重度肺损伤组(Ⅳ组)VT 40 ml/kg,机械通气2 h;极重度肺损伤组(Ⅴ组)VT 40 ml/kg,机械通气4 h.Ⅰ组在气管切开后即刻,其余各组在机械通气结束时采集腹主动脉血3 ml,并收集支气管肺泡灌洗液(BALF),测定血清和BALF中CC10蛋白水平;观察肺Clara细胞;计算肺湿/干重比(W/D).结果 Ⅳ组和Ⅴ组终末细支气管、呼吸细支气管管腔有大量脱落Clara细胞,血管壁有大量漏出的CC10蛋白,其余组上述表现不明显;Ⅱ组～Ⅴ组血清CC10蛋白水平逐渐升高,肺组织损伤程度逐渐加重(P＜0.05);与Ⅰ组、Ⅱ组和Ⅲ组比较,Ⅳ组和Ⅴ组BALF中CC10蛋白水平降低(P＜0.05);血清CC10蛋白水平与肺组织损伤程度和肺W/D呈正相关,相关系数分别为0.915和0.846(P＜0.01);BALF中CC10蛋白水平与肺组织损伤程度和肺W/D呈负相关,相关系数分别为-0.799和-0.816(P＜0.01).结论 血清CC10蛋白水平与大鼠呼吸机相关性肺损伤程度有关.     

吗啡后处理对大鼠离体心脏缺血再灌注损伤的影响

目的 评价吗啡后处理对大鼠离体心脏缺血再灌注损伤的影响.方法 雄性SD大鼠,体重180～200 g,应用Langendorff灌流装置,采用全心停灌45 min、再灌注60 min的方法制备大鼠离体心脏缺血再灌注模型.实验一:取模型制备成功的心脏32个,随机分为4组(n=8):Ⅰ组～Ⅳ组,Ⅰ组不予处理,Ⅱ组～Ⅳ组于再灌注即刻分别灌注含0.3、3.0和30 μmol/L吗啡的K-H液10 min,随后灌注正常K-H液50 min;实验二:根据实验一的结果,选择对离体心脏缺血再灌注损伤影响最强的吗啡浓度,另取模型制备成功的心脏32个,随机分为4组(n=8):Ⅰ组～Ⅳ组,Ⅰ组不予处理,Ⅱ组～Ⅳ组于再灌注即刻分别灌注含吗啡的K-H液5、10和20 min,随后灌注正常K-H液50 min;实验三:根据实验二的结果,选取对离体心脏缺血再灌注损伤影响最强的吗啡后处理方法.另取模型制备成功的心脏37个,随机分为5组:Ⅰ组(n=8)不予处理;Ⅱ组(n=8)、Ⅲ组～Ⅴ组(n=7)于再灌注即刻分别灌注含吗啡、10 μmol/L非选择性阿片受体阻断剂纳洛酮和吗啡、5 μmol/L选择性κ受体阻断剂nor-binahorphimine和吗啡、5 μmol/L选择性δ受体阻断剂naltrindole和吗啡的K-H液,各组均再灌注正常K-H液50 min.于再灌注60 min时测定心肌肌酸激酶同工酶(CK-MB)活性,计算心肌缺血危险区/梗塞区(IS/AAR).结果 根据实验一、二的结果于再灌注即刻灌注含3.0 μmol/L吗啡的K-H液10 min行后处理.实验三的结果:与Ⅰ组比较,Ⅱ组和Ⅴ组心肌IS/AAR和CK-MB活性降低,Ⅳ组心肌CK-MB活性降低(P<0.05或0.01),Ⅲ组以上指标差异无统计学意义(P>0.05);与Ⅱ组比较,Ⅲ组和Ⅳ组心肌IS/AAR和CK-MB活性升高(P<0.01),Ⅴ组上述指标差异无统计学意义(P>0.05).结论 吗啡后处理可减轻大鼠离体心脏缺血再灌注损伤,此作用可能与激活心肌κ受体有关.     

Comparison of blood-based and asanguineous cardioplegic solutions administered at 4 degrees C. An ultrastructural morphometric study in the dog

Although several studies have shown better myocardial preservation with blood-based than asanguineous cardioplegic solutions at myocardial temperatures above 15 degrees C, one might suspect that blood would become unsafe at lower temperatures because of increased oxygen-hemoglobin affinity and viscosity. We compared myocardial preservation in dogs subjected to 6 hours of aortic crossclamping and treated with modified Roe's asanguineous cardioplegic solution at 4 degrees C (group CA), blood cardioplegic solution at 4 degrees C (CB), or blood cardioplegic solution at 27 degrees C (WB, four dogs per group). Myocardial preservation was assessed by triphenyltetrazolium staining of whole hearts, and by analysis of ultrastructure and morphometric analysis of mitochondria in myocardial biopsies from three sites in each heart (left ventricle subepicardium and subendocardium and right ventricle). Tetrazolium staining showed no difference in preservation among the three treatment groups (no necrosis in any heart). For two of the three biopsy sites (left ventricular subepicardium and right ventricle), ultrastructural and morphometric analyses demonstrated signs of more severe subcellular injury in group CA than in CB (p = 0.013 to 0.004), whereas equivalent preservation with all treatments was observed in the left ventricular endocardial site. Functional recovery also appeared to be equivalent between treatments, to the extent that all dogs were successfully weaned from bypass after 20 minutes of reperfusion. We conclude that the safety and effectiveness of blood cardioplegia is not compromised by infusion at 4 degrees C compared with 27 degrees C and that myocardial preservation is not improved by using asanguineous cardioplegia instead of blood cardioplegia at 4 degrees C.     

A new concept of long-term donor heart preservation: nucleoside transport inhibition.

Myocardial ischemia results in a breakdown of adenosine triphosphate (ATP), which is associated with an accumulation of its catabolites adenosine and inosine. Adenosine is a potent but ineffective cardioprotective agent because it is rapidly transported to the endothelium and irreversibly catabolized. With the use of specific nucleoside transport inhibition (NTI), however, endogenous adenosine may accumulate at its site of production, and its further breakdown and washout on reperfusion is prevented. In this study we tested this concept and assessed the effect of NTI drug administration on 24 hours' preservation of donor hearts for transplantation. Twelve dogs were randomly allocated to two groups. In the first group (group 1, n = 6) the hearts were arrested with a cold hyperkalemic cardioplegic solution, excised and stored for 24 hours at 0.5 degrees C. After 24 hours the hearts were transplanted orthotopically. In group 2 (n = 6) the same procedure was followed, but a specific NTI agent was added to the cardioplegic solution (1 mg/L) and administered intravenously to the recipient dog before reperfusion of the transplanted heart (0.1 mg/kg). Despite maximal positive inotropic support, none of the control animals (group 1) could be weaned from cardiopulmonary bypass: within 1 hour irreversible cardiogenic shock occurred in all animals. In group 2 all hearts could be weaned from cardiopulmonary bypass and were hemodynamically stable without positive inotropic support. Serial transmural left ventricular biopsies revealed in group 1 moderate catabolism of ATP during cold storage. On reperfusion a further decline of the ATP content was seen, and the accumulated nucleosides were washed out.(ABSTRACT TRUNCATED AT 250 WORDS)     

Use of the Zung depression scale in patients with traumatic brain injury: 1 year post-injury

OBJECTIVE: The purpose of this study was to examine if the physical disabilities of patients with traumatic brain injury (TBI) would influence the assessment of depression when using the Zung depression scale. METHOD: Patients with TBI (n=59) were assessed 1 year after injury for depression by both a psychiatrist and the use of the Zung depression scale. RESULTS: By psychiatric evaluation, seven of 17 (41%) patients with severe TBI and one of 20 (5%) of the patients with moderate TBI were diagnosed with major depressive disorder. With the Zung depression scale, 10 of 17 (59%) patients with severe TBI met the cut-off (scored >55) for depression, whereas none of the patients with moderate (n=20) or mild (n=22) TBI did. The mean (SD) scores of the somatic scale were 2.91 (0.93), 2.49 (0.92) and 1.25 (0.43) for each group. The mean scores of the affective scale were 2.58 (0.90), 1.85 (0.79) and 1.24 (0.46). For patients with moderate (p<0.05) and severe (p<0.10) TBI, scores on the somatic items exceeded scores on their affective items. No difference in somatic and affective scale scores was noted for the patients with mild TBI. CONCLUSION: The increased endorsement of somatic results may be the somatic difficulties associated with traumatic brain injury.     

Acute severe postischemic myocardial depression reversed by triiodothyronine.

The purpose of this study was to determine the effects of triiodothyronine (T3) on postischemic left ventricular performance and high-energy phosphate content in a severe injury model. Isolated working rat hearts (n = 63) received 20 mL of hyperkalemic NIH No. 1 cardioplegia and were subjected to 20 minutes of ischemia at 37 degrees C. Treated hearts were reperfused with T3-supplemented modified Krebs-Henseleit buffer. Control hearts did not receive T3 supplementation. All treated hearts (n = 44) performed work after ischemia, whereas 26% (5/19) of the control hearts were not able to perform any left ventricular work after ischemia. Comparisons with preischemic values demonstrated significant progressive hemodynamic recovery with increasing concentrations of T3 (0, 0.06, 0.15, and 0.60 ng/mL) with concomitant recovery of left ventricular stroke work index (63%, 72%, 89% [p less than 0.05], and 99% [p less than 0.05], respectively). There were corresponding increases in recovery of aortic flow, systolic pressure, cardiac index, and stroke volume index (p less than 0.05). There were no significant changes in coronary sinus flow or heart rate in any group compared with preischemic values. Comparisons of postischemic high-energy phosphate concentrations also demonstrated no change between treated and untreated groups (p greater than 0.05). We conclude that administration of T3 in a severe left ventricular injury model significantly augments rapid ventricular recovery with no change in postischemic high-energy phosphate concentrations.     

Patterns of inflammation in mucosal biopsies of ulcerative colitis: perceived differences in pediatric populations are limited to children younger than 10 years

The histologic criteria used to diagnose ulcerative colitis in colonic mucosal biopsies have been established for many years and include crypt architectural distortion, plasmacellular infiltrates, and neutrophils in the crypt epithelium and lumen. In several recent studies, it has been noted that colonic mucosal biopsies from children presenting with ulcerative colitis show fewer histologic abnormalities at initial presentation, especially less architectural distortion, than do biopsies from adults. In this study, colonic mucosal biopsies taken at the time of presentation of ulcerative colitis in 15 adults and 25 children were examined blindly by two pathologists. All biopsies were taken prior to the initiation of therapy. Twelve children were between 1 and 10 years of age, and 13 children were between the ages of 11 and 17 years. All patients had at least 1 year of follow-up, with clinical and pathologic confirmation of the diagnosis of ulcerative colitis. Five separate histologic features that are characteristic of ulcerative colitis were scored on mucosal biopsies. Children < or = 10 years of age had significantly less crypt branching, plasma cells in the lamina propria, cryptitis, crypt abscesses, and epithelial injury than adults (P values ranging from < 0.0001 to 0.0032). Children between the ages of 11 and 17 years had less cryptitis, crypt abscesses, and epithelial injury than adults (P values ranging from 0.0001 to 0.007) but similar degrees of crypt architectural distortion and plasma cell infiltrates. For all histologic features examined except epithelial injury, the significant findings were due to differences in biopsies taken proximal to the rectum. No significant differences in histology scores were found in rectal biopsies between any age group, except for epithelial injury, which was significantly less in children < or = 10 years. The findings show for the first time that the perceived differences between adults and children with ulcerative colitis are largely due to a decrease in histologic features of colitis in children less than 10 years of age. As children approach adulthood, the degree of inflammation and architectural distortion seen is similar to that found in adults. However, rectal biopsies show similar degrees of colitis in all age groups.     

Ultrastructural study comparing the efficacy of five different methods of intraoperative myocardial protection in the human heart

The quality of myocardial protection during cardiac arrest in cardiac operations was investigated in 310 patients. Eighty patients underwent aortic valve replacement and 230 had coronary artery bypass grafting. Four different cardioplegic solutions (Kirsch, Bretschneider, St. Thomas' Hospital, and Hamburg) and the method of induced fibrillation were tested by ultrastructural analysis of the degree of ischemic injury at the end of the cardiac arrest period. Hypothermia was identical in all five groups. In this study, subendocardial and subepicardial needle biopsies were evaluated by a standardized scoring system. Chemical cardioplegia produced mainly moderate ultrastructural injury independent of the time of ischemia. Kirsch cardioplegia and the intermittent fibrillation procedure produced ischemic injury of greater and unpredictable severity. Only with Kirsch cardioplegia was a correlation observed between the duration of intraoperative arrest and the degree of injury, which is indicative of a lack of myocardial protection. The tolerance to ischemia was significantly better in patients undergoing bypass grafting than in those with aortic valve disease and therefore longstanding hypertrophy. In conclusion, the Bretschneider, St. Thomas' Hospital, and Hamburg solutions provide satisfactory myocardial protection but are not able to completely prevent myocardial ischemic injury. Kirsch cardioplegia and the intermittent fibrillation procedure provide insufficient myocardial protection. Patients with left ventricular hypertrophy are at a greater risk during cardiac operations than patients undergoing coronary bypass operations.     

Effects of halothane on arrhythmias induced by myocardial ischaemia

The effect of halothane on arrhythmias induced by ischaemia was investigated in rats, isolated perfused rat hearts, and pigs. Responses to the occlusion of the left anterior descending coronary artery were determined in groups (n = 9) of chronically prepared rats treated with no halothane, 0.5, or 1.0 per cent halothane immediately after occlusion; in isolated rat hearts (n = 10) treated with no halothane, 0.5, 1.0, 2.0, or 4.0 per cent halothane for 15 min before and after occlusion; and 20–25 kg pigs (n = 11) anaesthetised with halothane or pentobarbital. The ECG, arrhythmias, blood pressure (BP), heart rate (HR) and extent of infarction were determined in each model. In pigs, left ventricular pressure, dp/dt_max and cardiac output were also measured. In chronically prepared rats, halothane anaesthesia started after occlusion was antiarrhythmic and decreased the incidence of ventricular fibrillation and resulting mortality. In isolated rat hearts, 0.5 or 1.0 per cent halothane had little effect on occlusion-induced arrhythmias. The highest concentration of halothane increased the incidence of ventricular fibrillation both before and after occlusion. Halothane decreased developed ventricular pressure in a dose-dependent manner. In acutely prepared pigs, halothane pre-treatment had no appreciable effect upon occlusion-induced arrhythmias when compared with pentobarbital anaesthesia. Thus, halothane is antiarrhythmic when treatment is initiated after occlusion in the rat but this action is not seen in isolated hearts or intact pigs. The antiarrhythmic action of halothane is, therefore, species and model dependent.