Prevalence of myocardial ischemia as depicted by regional wall motion abnormality in blacks

Coronary artery disease with subsequent myocardial ischemia is a common cause of morbidity and mortality in the United States, and data are scarce on the prevalence of the disease in blacks. Regional wall motion abnormality correlates either directly or indirectly with myocardial ischemia. This study examines the two-dimensional (2-D) echocardiography of patients > or = 45 years for men and > or = 55 years at Metropolitan Nashville General Hospital, Nashville, Tennessee. A total of 601 2-D echocardiographic studies were performed on patients who presented with symptoms and signs of cardiovascular disease. Of these, 377 (62.7%) met the age criteria and formed the study group; 92 were excluded for various reasons, leaving 285 (75%) in the analysis group. A total of 80 (28.1%) patients had regional wall motion abnormality while 205 (71.9%) did not. On analysis of the 80 patients with regional wall motion abnormality, the segment of the heart commonly affected was the septal area, although more than one segment of the myocardium was affected in all of the patients. A total of 36 (45%) patients had normal left ventricular size. In relation to race, blacks had a higher prevalence of regional wall motion abnormality compared with whites (29.2% versus 26.2%, respectively), but the difference was not statistically significant. These prevalence rates indicate the importance of looking for this abnormality during echocardiographic evaluation of a patient. The presence of regional wall motion abnormality on 2-D echocardiography in the presence of other cardiovascular risk factors necessitates further investigation and management to minimize later complications of coronary artery disease.     

Cerebral protection by intermittent reperfusion during temporary focal ischemia in the rat

Temporary arterial occlusion has been routinely used as an adjunct in intracranial aneurysm surgery. This has commonly been performed using a protocol of multiple short periods of occlusion alternating with periods of restoration of normal circulation. Recently, the logical basis of this method has come under scrutiny. There is extensive experimental evidence to suggest that repetitive, brief periods of global ischemia may cause more severe cerebral injury than an equivalent single period of global ischemia. Only recently has this issue begun to be addressed with regard to focal ischemia. Hence, despite the common use of temporary clipping, little experimental data are available regarding the ischemic consequences of temporary arterial occlusion with periods of reperfusion versus uninterrupted temporary occlusion. To investigate this issue, a protocol of occlusion/reperfusion that simulates the temporal profile that occurs during surgery was performed in a rat model of focal ischemia. Sixteen anesthetized Sprague-Dawley rats were divided into two groups. The animals in Group I underwent 60 minutes of uninterrupted middle cerebral artery occlusion and the animals in Group II were subjected to six separate 10-minute occlusion periods with 5 minutes of reperfusion between occlusions. Histopathological analysis was performed 72 hours postischemia. Group I had significantly increased mean infarction volumes (50.0 +/- 12.1 mm3) compared to Group II (8.7 +/- 3.1 mm3) (p = 0.008). Injuries in Group I occurred in both the cortex and striatum, whereas Group II showed only striatal injuries. Furthermore, the extent of the injuries in Group II was less severe, characterized by ischemic neuronal injury rather than frank infarction. The results indicate that intermittent reperfusion is neuroprotective during temporary focal ischemia and support the hypothesis that intermittent reperfusion is beneficial if temporary clipping is required during aneurysm repair.     

Dobutamine-induced hypoperfusion without transient wall motion abnormalities: less severe ischemia or less severe stress?

We describe the first cDNA sequence encoding a juvenile hormone-specific epoxide hydrolase from an insect. A full-length cDNA clone revealed a 462-amino-acid open reading frame encoding an amino acid sequence with 44% identity and 64% similarity to human microsomal epoxide hydrolase. All residues in the catalytic triad (residues Asp227-His428-Asp350 in the M. sexta protein) were present, as was the conserved Trp154 corresponding to the oxyanion hole. The surprising similarity of insect juvenile hormone epoxide hydrolase to vertebrate microsomal epoxide hydrolases, coupled with the ancient lineage of the epoxide hydrolases and haloalkane dehalogenases, suggests that this catabolic enzyme evolved from an original ubiquitous detoxication function to a more recent role in hormonal regulation.     

Two dimensional echocardiographic analysis of wall motion abnormalities during handgrip exercise in patients with coronary artery disease

Studies were made of the feasibility and value of two dimensional echocardiography in detecting left ventricular asynergy during handgrip exercise in 45 patients with suspected coronary artery disease. Resting echocardiography revealed normal wall motion in 32 patients, and in 17 of these handgrip exercise induced abnormal wall motion. All 17 patients had significant stenoses in the coronary arteries. However, only 65 percent of patients with coronary artery disease whose resting two dimensional echocardiogram revealed normal wall motion showed abnormal wall motion during handgrip exercise. The left ventricular wall visualized in the short axis plane was divided into 5 segments, and a total of 225 segments were analyzed. Of 49 segments with exercise-induced asynergy, 46 (94 percent) reflected significant stenosis in the perfusing coronary artery. In particular, 16 (89 percent) of 18 segments with exercise-induced akinesia reflected stenosis of greater than 90 percent. Resting or exercise two dimensional echocardiography (or both) was able to diagnose multivessel disease with a predictability of 92 percent. It is concluded that two dimensional echocardiography combined with handgrip exercise has high specificity in detecting coronary artery disease and would be useful for predicting severely stenotic or multivessel coronary arterial lesions.     

Aortic root and left atrial wall motion. An echocardiographic study

The echocardiographically recorded movement of the aortic root was studied by analysing the relation between posterior aortic wall motion and other intracardiac events. The systolic anterior movement of the aortic root continued beyond aortic valve closure and in cases with mitral regurgitation began significantly earlier than in normal subjects. The diastolic rapid posterior movement began after mitral valve opening but did not occur in patients with mitral stenosis. The total amplitude of aortic root motion was increased in patients with mitral regurgitation, diminished in cases of mitral stenosis, and was normal with aortic regurgitation. In patients with atrioventricular block an abrupt posterior movement followed the P wave of the electrocardiogram irrespective of its timing in diastole. These observations correlate with the expected changes in left atrial volume during the cardiac cycle both in the normal subjects and patients with heart disease. The results support the hypothesis that phasic changes in left atrial dimension are largely responsible for the echocardiographically observed movement of the aortic root and indicate a potential role for echocardiography in the analysis of left atrial events.     

Role of glutathione in hepatic bile formation during reperfusion after cold ischemia of the rat liver

BACKGROUND/AIMS: Liver reperfusion following cold ischemia is frequently associated with diminished bile flow in patients undergoing liver transplantation. Glutathione is a major determinant of bile-acid independent bile flow, and the effects of cold ischemia on biliary glutathione excretion are unknown. METHODS: We examined the effects of cold ischemia (University of Wisconsin solution (4 degrees C), 24 h) with subsequent reperfusion (100 min) on biliary glutathione excretion in a recirculating system. Since glutathione might represent an important antioxidant within the biliary tract and oxidative stress in the biliary tract during reperfusion could contribute to the pathogenesis of bile duct injury after liver transplantation, we also assessed bile duct morphology in reperfused livers of mutant TR- -rats, in whom biliary excretion of glutathione is already impaired. RESULTS: Hepatic bile formation was diminished in reperfused Wistar rat livers after cold ischemia. Biliary glutathione concentrations and output were significantly decreased and correlated with postischemic changes in bile secretion. An increased biliary oxidized glutathione/glutathione ratio, indicating oxidative stress, was detected only immediately after the onset of reperfusion. Basal bile flow rates in TR- -rat livers which were already markedly reduced in control-perfused livers, decreased further during the early but not the later reperfusion period. Reperfusion of both Wistar and TR- -rat livers was not associated with electron microscopic evidence of bile duct damage. CONCLUSIONS: We conclude that impaired biliary excretion of glutathione contributes to decreased bile flow after cold ischemia. The absence of biliary glutathione does not appear to promote ultrastructural evidence of bile duct injury during reperfusion in the isolated perfused rat liver.     

Comparison of echocardiographic acoustic quantification system and radionuclide ventriculography for estimating left ventricular ejection fraction: validation in patients without regional wall motion abnormalities

We studied the presence of high-level resistance to aminoglycosides, penicillin tolerance and glycocalyx production in 160 isolates of Streptococcus mutans. Susceptibility to amoxycillin, cefazolin, imipenem, erythromycin, clindamycin, vancomycin and teicoplanin was also investigated. Of the isolates analysed, 58.8% produced glycocalyx in vitro and 2.5% were penicillin-tolerant. High-level resistance to streptomycin was found in 16.3% of the isolates, but all were sensitive to all other antibiotics tested. We found no significant relationship between glycocalyx production and high-level streptomycin resistance, penicillin tolerance or antibiotic susceptibility, except for a greater susceptibility to clindamycin and vancomycin in isolates that produced glycocalyx. Although our findings reflect the clinically favourable pattern of susceptibility currently found in this species, the appearance in some isolates of resistance, tolerance and glycocalyx production should be investigated because of the risks involved in endocarditis caused by S. mutans.     

Evaluation of regional left ventricular wall motion with color kinesis: comparison with two-dimensional echocardiography in patients after acute myocardial infarction

BACKGROUND: Color kinesis (CK) is a new echocardiographic technique for the assessment of left ventricular (LV) wall motion based on acoustic quantification. Using integrated backscatter data, this technique identifies the pixel value transitions from blood to myocardial tissue throughout systole and tracks endocardial motion in real time. The color-encoded images, built on a frame-by-frame basis by adding one color at a time, provide an integrated display of the timing and amplitude of endocardial motion in a single end-systolic frame. Recent studies have shown that CK is a promising clinical tool for quantitative assessment of regional LV function. OBJECTIVES: The aim of this study was to evaluate the feasibility and accuracy of CK in identifying the regional wall-motion abnormalities diagnosed by conventional two-dimensional (2-D) echocardiography in patients after acute myocardial infarction (AMI). METHODS: The end-systolic color overlays were analyzed using a method to quantify the regional timing and amplitude of endocardial systolic excursion (ESE) based on the count of the numbers of colors. At this point, the total duration (ESE timing) and distance (ESE amplitude) of endocardial excursion from end-diastolic to end-systolic color-frame was calculated in each segment. In 54 patients after AMI, we compared the feasibility and ability of CK superimposed on 2-D superimposed on 2-D superimposed on 2-D echocardiographic images and visual 2-D echo analysis to evaluate the endocardial border excursion in parasternal short-axis (SAX) and apical four-(AP4CH) and two-(AP2CH) chamber views. In 20 normal subjects, the end-systolic color overlays were used to evaluate the variability of the measurements of ESE timing (msec) and amplitude (cm) and to define the reference values. Image quality was considered adequate if at least 12 of 16 segments could be evaluated for systolic function by conventional visual 2-D echo. Among 54 patients, 35 with adequate studies were selected to determine the accuracy of quantitative analysis of CK images in identifying regional wall-motion abnormalities. RESULTS: The SAX view was obtained in 36 of 54 patients; of the possible 216 segments, 210 (97%) were adequately visualized by 2-D echocardiography and 207 (96%) by CK. Apical views were obtained in 50 patients (93%); of the possible 300 segments, 93% were visualized by 2-D echocardiography and 90% by CK in the AP4CH view and 94% and 92%, respectively, were visualized by the two methods in the AP2CH view. In normal subjects, measurements of ESE timing and amplitude were found to be consistent and the mean values were 346 msec (range 280-360) and 0.99 cm (range 0.72-1.26) respectively. In the 35 selected patients, 2-D echocardiography identified 355 normokinetic segments in which ESE timing and amplitude were similar to the reference values. In 83 hypokinetic segments and 108 akinetic segments, ESE timing and amplitude were significantly inferior to values of normokinetic segments (p < 0.001). An ESE timing below the reference values of 280 msec identified all of the 191 asynergic segments (sensitivity and specificity = 100%) and an ESE amplitude of less than 0.70 cm identified 188 asynergic segments (sensitivity = 98% and specificity = 99%). CONCLUSIONS: CK showed good feasibility and diagnostic accuracy in identifying regional wall motion abnormalities in patients with acute myocardial infarction. The model used in our study for the quantitative analysis of color kinesis images, which provided easy and feasible indices of timing and amplitude of endocardial excursion, enabled fast and objective evaluation of LV regional wall motion.     

Downregulation of calpastatin in rat heart after brief ischemia and reperfusion

The activities of calpain and its endogenous inhibitor, calpastatin, were measured in the soluble fraction of perfused rat heart after ischemia for 5-20 min and reperfusion for up to 30 min. The method for m-calpain measurement was modified: washing of the DEAE-cellulose column with 0.18 M NaCl instead of 0.15 M NaCl increased the m-calpain activity 12.5-fold. Ischemia for 20 min followed by reperfusion for 30 min did not affect the m-calpain activity but decreased the calpastatin activity. m-Calpain was enriched in the nucleus-myofibril fraction but was not further translocated on ischemia-reperfusion. Mu-calpain was below the limit of detection on immunoblotting or casein zymography, but its mRNA was substantially expressed, as detected on Northern blotting. Casein zymography also revealed a novel Ca2+-dependent protease without the typical characteristics of mu- or m-calpain. The immunoblotting of myocardial fractions showed that calpastatin was proteolyzed on ischemia-reperfusion. The calpastatin proteolysis was suppressed by a calpain inhibitor, Ac-Leu-Leu-norleucinal. Calpastatin may sequester calpain from its substrates in the normal myocardium, but may be proteolyzed by calpain in the presence of an unidentified activator in the early phase of calpain activation during ischemia-reperfusion, resulting in the proteolysis of calpastatin and then other calpain substrates.     

Pathogenesis of ischemia reperfusion injury of the kidney after transient renal arterial clamping in rats

Renal function can be severely impaired through injuries sustained after both short and prolonged periods of complete ischemia. The magnitude of renal dysfunction resulting from these conditions and their reversibility depend on the duration of anoxia. In this study, we used a Sprague-Dawley rat model (5 to 7 rats in each group) to study the pathogenesis of short-term ischemia (30, 60, and 120 min)/reperfusion (2, 4, 24 h, 1 wk, and 3 wk) injury of the kidney under warm (room temperature) or cold (4 degrees C) conditions. Ischemia was induced by clamping the renal artery. Changes in kidney weight, histopathology, concentrations of serum thromboxane and leukotriene, and tissue malonyldialdehyde (MDA) concentration, numbers of apoptotic bodies, and p53 expression in the kidney were compared with those of sham-operated rats. The results showed that the immediate increase in kidney weight due to inflammatory swelling was associated with simultaneous elevation of serum thromboxane and leukotriene levels. The changes in mediator levels were closely related to the duration of ischemia and temperature. Histologic structures were preserved better when renal artery clamping was done at 4 degrees C. MDA peroxidation products from the ischemic tissue prominently increased 1 week following ischemia; this paralleled a secondary increase in leukotriene levels. Flow cytometric detection of p53 oncoprotein showed a marked increase at 1 week following ischemia, which was accompanied by the development of apoptotic bodies in ischemic tissues. These changes were also closely related to the ischemic time and temperature during ischemia. This animal model may be useful for future studies of the prevention of ischemia/reperfusion injury of the kidney and for selection of effective antioxidants.     

Tumor necrosis factor-alpha in ischemia and reperfusion injury in rat lungs

The effects of both recombinant rat tumor necrosis factor-alpha (TNF-alpha) and an anti-TNF-alpha antibody were studied in isolated buffer-perfused rat lungs subjected to either 45 min of nonventilated [ischemia-reperfusion (I/R)] or air-ventilated (V/R) ischemia followed by 90 min of reperfusion and ventilation. In the I/R group, the vascular permeability, as measured by the filtration coefficient (Kfc), increased three- and fivefold above baseline after 30 and 90 min of reperfusion, respectively (P < 0.001). Over the same time intervals, the Kfc for the V/R group increased five- and tenfold above baseline values, respectively (P < 0.001). TNF-alpha measured in the perfusates of both ischemic models significantly increased after 30 min of reperfusion. Recombinant rat TNF-alpha (50,000 U), placed into perfusate after baseline measurements, produced no measurable change in microvascular permeability in control lungs perfused over the same time period (135 min), but I/R injury was significantly enhanced in the presence of TNF-alpha. An anti-TNF-alpha antibody (10 mg/rat) injected intraperitoneally into rats 2 h before the lung was isolated prevented the microvascular damage in lungs exposed to both I/R and V/R (P < 0.001). These results indicate that TNF-alpha is an essential component at the cascade of events that cause lung endothelial injury in short-term I/R and V/R models of lung ischemia.     

Effect of endogenous nitric oxide on energy metabolism of rat heart mitochondria during ischemia and reperfusion

The effects of ischemia and postischemic reperfusion on the functions of the heart and its mitochondria were studied with special attention to the effect of nitric oxide (NO) by treatment of rat hearts with the nitric oxide synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) or its noninhibitory isomer N(G)-nitro-D-arginine methyl ester (D-NAME). NO generated during reperfusion caused increase in coronary flow (CF), but had no effect on the left ventricular pressure (LVP) or heart rate (HR). The ATP level of the heart decreased during ischemia and was not completely restored by introduction of oxygen during reperfusion due to damage of complexes I and II of the respiratory chain of mitochondria by NO. Inhibition of the respiratory chain resulted in generation of hydrogen peroxide, and NO and NO-derived species generated after production of NO caused further damage of various proteins in mitochondria, such as complexes I and II of the respiratory chain and pyruvate dehydrogenase (PDH). These results suggested that NO generated on reperfusion was the primary cause of mitochondrial dysfunction by damage of complexes I and II of the respiratory chain, with consequent increase of CF in the heart.     

Long-term recovery of regional wall motion in patients with medically treated anterior myocardial infarction: quantitative assessment of the post-infarction left ventriculograms

Contrast sensitivity has been shown to be affected in Alzheimer's disease (Ad). We investigated low contrast acuity and contrast sensitivity using clinical test charts in this patient population. Additionally, we tested patients with vascular dementia (vd) and mixed dementia (md), (Alzheimer' with vascular dementia). Contrast sensitivity was assessed using the Vistech VCTS 6500 test chart. Low contrast acuity was measured using the Regan charts at four contrast levels (96%, 50%, 25% and 11%). The patient population consisted of 19 Ad patients, 9 vd patients and 10 md patients. Reduction in acuity was found with contrast level in all cases. Regression lines were fit to the data and statistical analysis was performed. We did not find a statistically significant difference between the Ad and vd or md groups. We did, however, find a difference between the vd and md groups. We did find reduction in contrast sensitivity at all spatial frequencies when compared to the elderly normal. Correspondingly, we found a significant difference in acuity when compared with normal data at the four contrast levels tested. Acuity is reduced with contrast in all patient groups. Our contrast sensitivity results are similar to those reported in the literature. This study points out the importance of using simple clinical test charts and further underscores the idea that there is a primary visual deficit in Ad.     

Brainstem auditory evoked potentials during brainstem ischemia and reperfusion in gerbils

To evaluate the reversibility of neural function in the brainstem following ischemia, we investigated the effect of transient brainstem ischemia on the brainstem auditory evoked potential in gerbils. Brainstem ischemia was produced by bilateral extracranial occlusion of vertebral arteries. Local cerebral blood flow was measured by quantitative autoradiography after 5 min of ischemia and was reduced to less than 3 ml/100 g per min in the pons and lower midbrain, indicating severe and reproducible brainstem ischemia. During brainstem ischemia, brainstem auditory evoked potential waveforms disappeared completely. After a brief ischemic insult (5 min), all four brainstem auditory evoked potential components recovered to normal. After longer ischemic insults (10-30 min), brainstem auditory evoked potential components never recovered to normal. Microtubule-associated protein 2 immunoreactivity revealed differential vulnerability of the acoustic relay nuclei in the brainstem. Neurons in the lateral lemniscus were most vulnerable, followed in order by neurons in the trapezoid body, the superior olive and the cochlear nucleus. We also demonstrated a close relationship between the reversibility of ischemia-induced changes on brainstem auditory evoked potential and ischemic lesions of these relay nuclei. These data may be useful for evaluating the therapeutic window of thrombolytic therapy during acute vertebrobasilar occlusion.     

Activation of c-Jun N-terminal kinase during ischemia and reperfusion in mouse liver

We have generated a mouse model for hepatic ischemia in which surgical subcutaneous transposition of the spleen allows hepatic ischemia to be applied without affecting other tissues. Using this mouse model we investigated the relationship between the length of ischemic periods in the liver and subsequent liver function; furthermore, we assayed the activation of c-Jun N-terminal kinase (JNK) during ischemia and reperfusion. Although prior to this study only the activated form of JNK was known to be translocated to the nucleus, we found that JNK translocates to the nucleus during ischemia without activation and is then activated during reperfusion. These results suggest a novel mechanism of JNK activation.     

Transoesophageal echocardiographic assessment of haemodynamic function during laparoscopic cholecystectomy

We have measured cardiovascular changes associated with insufflation of carbon dioxide and the reverse Trendelenburg position during laparoscopic cholecystectomy, using transoesophageal echocardiography in 13 healthy patients. End-tidal carbon dioxide values increased after insufflation of carbon dioxide, with values significantly (P < 0.05) increased after lateral tilt positioning. Creation of a pneumoperitoneum was associated with increases (P < 0.05) in left ventricular end-systolic wall stress, concomitant with increases (P < 0.01) in peak airway pressure and systemic arterial pressure. In addition, left ventricular end-diastolic area decreased (P < 0.05) after reverse Trendelenburg positioning. Left ventricular ejection fraction was maintained throughout the study.     

Importance of endogenous adenosine during ischemia and reperfusion in neonatal porcine hearts

BACKGROUND: Adenosine has several potentially cardioprotective effects. We hypothesized that the effects of endogenous adenosine vary with degree of ischemia and that elevating endogenous levels is protective. METHODS AND RESULTS: Isolated blood-perfused piglet hearts underwent 120 minutes of low-flow ischemia (10% flow) or 90 minutes of zero-flow ischemia, all with 60 minutes of reperfusion. Hearts were treated with either saline, the adenosine receptor blocker 8-sulfophenyltheophylline (8SPT, 300 micromol x L(-1)), or the nucleoside transport inhibitor draflazine (1 micromol x L(-1)). In separate groups, biopsies were obtained before and at the end of ischemia. Compared with saline, 8SPT did not significantly alter functional recovery in either protocol. Draflazine significantly improved percent recovery of left ventricular systolic pressure both in the low-flow protocol (92+/-3% versus 75+/-2% [saline] and 73+/-3% [8SPT], P<.001 for both) and in the zero-flow protocol (76+/-3% versus 59+/-4% [saline] and 46+/-9% [8SPT], P<.05 for both). In the zero-flow protocol, draflazine also significantly reduced ischemic contracture and release of creatine kinase. Tissue adenosine at the end of ischemia was elevated by draflazine compared with saline-treated hearts: after low-flow ischemia to 0.10+/-0.05 versus 0.00+/-0.00 micromol x g(-1) dry wt (P<.05) and after zero-flow ischemia to 1.73+/-0.82 versus 0.15+/-0.03 micromol x g(-1) dry wt (P<.05). CONCLUSIONS: In neonatal porcine hearts, endogenous adenosine produced during ischemia does not influence ischemic injury or functional recovery. Elevating endogenous adenosine by draflazine elicits cardioprotection in both low-flow and zero-flow conditions.     

Modulation of adenosine effects in attenuation of ischemia and reperfusion injury in rat heart

We investigated whether xanthine oxidase-derived superoxide radical generation could be modified by interfering with adenosine transport and metabolism in reducing myocardial injury during post-ischemic reperfusion. Isolated rat hearts perfused at constant pressure were subjected to 20 min of pretreatment with test agents, followed by 40 min global ischemia and 30 min reperfusion with or without test agents. In hearts treated with adenosine deaminase inhibitor, erythro 9-(2-hydroxy-3-nonyl) adenine (EHNA), alone or together with a selective nucleoside transport blocker, p-nitrobenzylthioinosine (NBMPR), the accumulated amount of O-2. was significantly reduced [10.2+/-0.97, 11.6+/-2.4, 8.1+/-0.51, respectively, v 31.6+/-2.1 (s. e.) nmol/wet g/30 min in ischemic control, P<0.01]. A positive correlation between O-2. and inosine release was observed in the initial 5 min of reperfusion in hearts treated with either EHNA or NBMPR ( r=0.475, P<0.05). Furthermore, the accumulated amount of LDH release showed positive correlation with that of O-2. among the same groups (r=0.474, P<0.05). Both EHNA and NBMPR had the cardioprotective effect on the recovery of left ventricular end-diastolic pressure (LVEDP), ATP repletion, and build up of endogenous adenosine. This study suggests that : (1) adenosine metabolism can be manipulated towards the formation of O-2. during reperfusion, and it has an important bearing on the cardiac recovery of ischemic myocardium, (2) the generation of O-2. is related to only inosine release during initial reperfusion.