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ROMK inwardly rectifying ATP-sensitive K+ channel. I. Expression in rat distal nephron segments.

The inwardly rectifying, ATP-sensitive K+ channel (ROMK) was localized by in situ hybridization in the rat kidney. Tissue in situ hybridization revealed that transcripts encoding the ROMK channel were expressed predominantly in cortical and outer medullary nephron segments. The localization of ROMK mRNA to specific nephron segments was assessed by hybridization of isolated nephron segments with an ROMK-specific probe (single segment in situ hybridization). ROMK mRNA was present in cortical and medullary thick ascending limb, distal tubule, and cortical and outer medullary collecting ducts, but not in proximal tubule. A weak hybridization was observed with inner medullary collecting ducts. To confirm these results, serial cryosections were alternatively stained by hybridization histochemistry for ROMK mRNA or by immunocytochemistry using antibodies specific for S1, S2, or S3 proximal tubular segments. Tubular cells that displayed immunoreactivity with the proximal tubular segment-specific antibodies showed little, if any, ROMK message. In addition, using an in situ hybridization and immunocytochemistry double-labeling technique, ROMK transcripts and vitamin D-dependent calcium-binding protein were shown to colocalize to the distal tubule (distal convoluted tubule and connecting tubule). The overall nephron localization of ROMK mRNA shown in these studies is consistent with the possibility that this novel channel may represent the low-conductance ATP-sensitive K+ channel that has been identified in apical membranes of thick limb and collecting duct segments and is believed to participate in K+ secretion.

Animals↗

Absorption from different intestinal segments during exercise.

This study evaluated intestinal absorption from the first 75 cm of the proximal small intestine during 85 min of cycle exercise [63.6 +/- 0.7% peak O2 consumption (VO2 peak)] while subjects ingested either an isotonic carbohydrate-electrolyte beverage (CHO-E) or a water placebo (WP). The CHO-E beverage contained 117 mM (4%) sucrose, 111 mM (2%) glucose, 18 meq Na+, and 3 meq K+. The two experiments were performed a week apart by seven subjects (6 men and 1 woman; mean VO2 peak = 53.5 +/- 6.5 ml . kg-1 . min-1). Nasogastric and multilumen tubes were fluoroscopically positioned in the gastric antrum and duodenojejunum, respectively. Subjects ingested 23 ml/kg body weight of the test solution, 20% (383 +/- 11 ml) of this volume 5 min before exercise and 10% (191 +/- 5 ml) every 10 min thereafter. By using the rate of gastric emptying (18.1 +/- 1.1 vs. 19.2 +/- 0. 7 ml/min for WP and CHO-E, respectively) as the rate of intestinal perfusion, intestinal absorption was determined by segmental perfusion from the duodenum (0-25 cm) and jejunum (25-50 and 50-75 cm). Water flux was different (P < 0.05) between solutions in the 0- to 25- and 25- to 50-cm segments for WP vs. CHO-E (30.7 +/- 2.7 vs. 15.0 +/- 2.9 and 3.8 +/- 1.1 vs. 11.9 +/- 3.3 ml . cm-1 . h-1, respectively). Furthermore, water flux differed (P < 0.05) for WP in a comparison of the 0- to 25- to the 25- to 50-cm segment. Total solute flux (TSF) was not significantly different among segments for a given solution or between solutions for a given segment. There was no difference between trials for percent change in plasma volume. These results indicate that 1) fluid absorption in the proximal small intestine depends on the segment studied and 2) solution composition can significantly effect water absorption rate in different intestinal segments.

Adult↗

Segmental organization of visceral and somatic input onto C3-T6 spinothalamic tract cells of the monkey.

1. Referred pain of visceral origin has three major characteristics: visceral pain is referred to somatic areas that are innervated from the same spinal segments as the diseased organ; visceral pain is referred to proximal body regions and not to distal body areas; and visceral pain is felt as deep pain and not as cutaneous pain. The neurophysiological basis for these phenomena is poorly understood. The purpose of this study was to examine the organization of viscerosomatic response characteristics of spinothalamic tract (STT) neurons in the rostral spinal cord. Interactions were determined among the following: 1) segmental location, 2) effects of input by cardiopulmonary sympathetic, greater splanchnic, lumbar sympathetic, and urinary bladder afferent fibers, 3) location of excitatory somatic field, e.g., hand, forearm, proximal arm, or chest, 4) magnitude of response to hair, skin, and deep mechanoreceptor afferent input, and 5) regional specificity of thalamic projection sites. 2. A total of 89 STT neurons in segments C3-T6 were characterized for responses to visceral and somatic stimuli. Neurons were activated antidromically from the contralateral ventroposterolateral oralis or caudalis nuclei of the thalamus. Cell responses to visceral and somatic stimuli were not different on the basis of the thalamic site of antidromic activation. Recording sites for 61 neurons were located histologically; 87% of lesion sites were located in laminae IV-VII or X. There was no relationship between response properties of the neurons and spinal laminar location. 3. Different responses to visceral stimuli were observed in three zones of the rostral spinal cord: C3-C6, C7-C8, and T1-T6. In C3-C6, urinary bladder distension (UBD) and electrical stimulation of greater splanchnic and lumbar sympathetic afferent fibers inhibited STT cells. Electrical stimulation of cardiopulmonary sympathetic afferents increased cell activity in C5 and C6 and either excited or inhibited STT cells in C3 and C4. In the cervical enlargement (C7-C8), STT cells generally were either inhibited or showed little response to stimulation of visceral afferent fibers. In T1-T6, input from greater splanchnic and cardiopulmonary sympathetic afferent nerves increased activity of STT cells. Lumbar sympathetic afferent input inhibited cells in T1-T2 and had little effect on cells in T3-T6, whereas UBD decreased cell activity in all segments studied. 4. In general, stimulation of somatic structures increased activity of STT neurons in segments that received primary afferent innervation from the excitatory somatic receptive field or in the segments immediately adjacent to these segments. Only input from the forelimb, especially the hand, markedly excited cells in C7 and C8.+

Afferent Pathways↗

Clonal expansion of T-cell receptor beta gene segment in the retrocochlear lesions of EAE mice.

It has been reported that the T cell receptor V beta 8.2 (TcrbV8.2) gene segment is predominantly expressed in encephalomyelitic T cells responding to myelin basic protein (MBP) in experimental allergic encephalomyelitis (EAE) mice. We have demonstrated retrocochlear hearing loss in EAE mice in previous studies. Administration of a monoclonal antibody specific to the T cell receptor V beta 8 (TcrbV8) subfamily prevented both this type of hearing loss and the central nerve disease. In this study, we examined the role of the TcrbV8.2 gene segment in the retrocochlear lesions of EAE mice. A clonal expression of T cell receptor beta chain gene segment (TcrbV8.2-TcrbD2-TcrbJ2.7) was identified in the retrocochlear lesions. The TcrbV8.2 gene segment appears to recombine only with TcrbJ2.1 (32.1%) and TcrbJ2.7 (67.9%) gene segments. The TcrbJ2.7 gene segment has also been previously identified as the dominant TcrbJ gene in the lymph nodes of EAE mice. Only TcrbD2, with a length of 4 amino acids, was observed recombining with these TcrbV8.2 sequences. G and C nucleotides are predominantly expressed at the N regions between the V-D and D-J junctions. This dominant TcrbV gene segment (TcrbV8.2-TcrbD2-TcrbJ2.7) observed in the retrocochlear lesions has been identified in the MBP-specific T cells from the lymph nodes of EAE mice. These results suggest that a small subset of antigen-specific T cells migrate to, and expand at, the retrocochlear lesions, which leads to hearing loss.

Amino Acid Sequence↗

Implications of differences in coiling indices at different segments of the umbilical cord.

The purpose of this study was to find out if the coiling density is similar in all segments of term singleton umbilical cords. We compared the coiling index (coils/cm) at three different segments of 159 cords. There was no statistical difference between the coiling indices of the placental and middle segment, but significantly increased coiling was found at the fetal end compared with the placental and middle segments. Coiling indices were not significantly correlated with gestational age, cord length or birth weight. We diagnosed concordant hypo- and hypercoiling when the placental and fetal segments had the same density classification, and discordant hypo- and hypercoiling when these segments had different density classifications. Concordant hypocoiling and hypercoiling were found in 4.4 and 6.3% of the cords examined, respectively (total of 10.7%), concordant normal coiling in 95 (59.7%) and discordant density classifications in 29.6%. We concluded that the coiling index should be established in two distinct segments and that the spatial configuration of the coils, which protects the blood flow in the umbilical cord, might not be measured by coil density only.

Birth Weight↗

Darier disease with paired segmental manifestation of either excessive or absent involvement: a further step in the concept of twin spotting.

For the first time, we describe a case of type 2 segmental Darier disease with concomitant band-like areas of healthy skin. This clinical observation gives a further hint for the understanding of type 2 segmental manifestations in autosomal dominant diseases. We had observed a 17-year-old patient with Darier disease since the age of 13 years. On the frontal aspect of his body, the lesions were found to be diffusely and rather symmetrically disseminated. On the back, however, a band-like pattern of pronounced involvement with concomitant streaks of healthy skin, both following the lines of Blaschko, was noted. Type 2 segmental manifestation of autosomal dominant disorders can be explained by the assumption that the individual carries a germline mutation that gives rise to a diffuse, nonsegmental distribution of the disease. In addition, a postzygotic mutation occurring at an early developmental stage would result in loss of heterozygosity and give rise, in a segmental area, to a homozygous or hemizygous state of the mutation. This would explain the enhanced severity of the segmental lesions. Theoretically, an early event of mitotic recombination should give rise, simultaneously, to a clone of cells that are homozygous for the corresponding wild-type allele, and for this reason paired segmental areas of either excessive or absent involvement, in the form of twin spotting, should occur on the background of an ordinary, nonsegmental phenotype, as exemplified by Happle and König in a case of epidermolytic hyperkeratosis of Brocq. These authors stated that, in autosomal dominant skin disorders, segmental areas of healthy skin will usually be difficult to recognize. This may explain why such a twin spot phenomenon has so far not been encountered in Darier disease.

Acitretin↗

Does chronic ST segment elevation following Q wave myocardial infarction exclude tissue viability?

PURPOSE: Electrocardiographic (ECG) ST segment elevation lasting 2 or more weeks following Q wave myocardial infarction has been associated with 'ventricular aneurysm' and absence of tissue viability. Regional systolic dysfunction may reflect either viable myocardium or scar. Positron emission-tomographic (PET) imaging can distinguish viable from nonviable tissue. We hypothesized that patients with chronic ST segment elevation after Q wave infarction might demonstrate salvageable myocardium in the infarct region. METHODS: The ECGs of 1,229 sequential patients undergoing PET scans for viability assessment were reviewed by an electrocardiographer to identify individuals with chronic anteroseptal Q wave infarctions with persistent ST segment elevation exceeding 1 mV. Patients with QRS duration longer than 0.14 ms or rhythm other than sinus were excluded. Viability was considered present if either a reversible stress-induced perfusion defect (ischemia) or a resting perfusion-metabolism mismatch (hibernation) was identified. RESULTS: Anteroseptal ECG Q wave infarction was identified in 132 subjects (74% male, age 61 +/- 12 years). Chronic ST segment elevation was present in 84 subjects (64%) and absent in 48. Baseline clinical characteristics and left ventricular systolic function were similar in both groups. 63% of those with and 56% of those without chronic ST elevation had viable myocardium. No relationship was noted between chronic ST segment elevation and the presence or absence of myocardial viability. CONCLUSIONS: Chronic ST segment elevation after anteroseptal Q wave myocardial infarction does not exclude myocardial viability in the 'infarct zone'. Evaluation of residual tissue viability is indicated to assess the benefit of revascularization in patients with Q wave infarction and chronic ST segment elevation.

Aged↗

Outcomes and indications of segmental pancreatectomy. Comparison with distal pancreatectomy.

BACKGROUND/AIM: To preserve pancreatic function, segmental pancreatectomy has been proposed for benign or low-malignancy tumors in the pancreatic body. Indications for the procedure, however, are still controversial. METHODS: In this study, we investigated the advantages and disadvantages of segmental pancreatectomy compared with distal pancreatectomy and subsequently determined indications for segmental pancreatectomy. RESULTS: The distal pancreatectomy patients had shorter operation times, lower incidence of operative complications, and shorter hospital stays compared to segmental pancreatectomy patients. Endocrine function in distal pancreatectomy patients deteriorated compared to that of segmental pancreatectomy patients. The postoperative 75-gram oral glucose tolerance test showed a diabetic pattern in 3 of 7 distal pancreatectomy patients, whereas none of the segmental pancreatectomy patients became diabetic after surgery. The relation between the length of the removed pancreas and plasma glucose at 2 h after the 75-gram glucose intake showed a significant correlation. CONCLUSION: According to our results, if the length of removed pancreas is longer than 12 cm, the patients will have a risk of acquiring diabetes. In those cases, the segmental pancreatectomy should be considered.

4-Aminobenzoic Acid↗

Celiprolol, a compound which attenuates myocardial acidosis and improves regional segmental function following ischemia in dogs: a comparison with propranolol.

Celiprolol, propranolol or saline were administered to separate groups (n = 5-6) of anesthetized dogs in which a critical stenosis was applied to the circumflex coronary artery for 90 min and then reperfused for 30 min. Test drugs were administered at 30 min poststenosis and the effects on pH, regional function and endocardiogram were monitored. A reduction in coronary flow of 54 +/- 2% (n = 27) yielded marked increases in hydrogen ion concentration (H+) of 17 +/- 2 X 10(-8) and ischemic endocardial ST segment of 6 +/- 1 mV while ischemic segmental shortening decreased 75 +/- 9%. Heart rate, arterial pressure and normal regional function were not altered. Celiprolol 0.1 and 1 mg/kg, i.v., reversed the alterations in H+ and ischemic ST segment to prestenosis values while improving ischemic segmental shortening 20 and 38%, respectively, and not affecting heart rate. Propranolol 0.1 and 1 mg/kg, i.v., reversed the alterations in H+ and ischemic ST segment to prestenosis values while further decreasing ischemic segmental shortening 66 and 30%, respectively. Upon reperfusion, ischemic segmental shortening returned to prestenosis values in the group treated with celiprolol 1 mg/kg, i.v., while the propranolol- and saline-treated groups further decreased. It is concluded that celiprolol is efficacious in normalizing myocardial function and ischemia-induced electrophysiological changes following coronary artery stenosis.

Acidosis↗

Function of somite and somitocoele cells in the formation of the vertebral motion segment in avian embryos.

We have studied the distribution of thoracic somite and somitocoele-derived cells using homotopical grafting between quail and chicken embryos and reincubation periods of 2-6 days. Serial sections were evaluated with antibodies against quail cells, quail hemangiopoietic cells and desmin. With the exception of neural crest cells in the cranial sclerotome half, all cells of the operated segment are quail cells derived from a single somite. These cells differentiate into sclerotome, myotome and the anlage of the dermis of the back. After longer reincubation periods, the somite-derived quail cells form the neighboring halves of 2 adjacent vertebral bodies and the intervening (disc-homologous) tissue. Resegmentation is furthermore visible in the lamina and the spinous process. Somite cells also form the articular and transverse processes, and the intertransverse muscle including its insertion to the next cranial transverse process. One thoracic somite forms the proximal part of 1 rib. In more distal parts, 1 somite forms the cranial half of 1 rib and the caudal half of the next cranial rib, and the intercostal muscle and part of the connective tissue. Somite-derived quail cells are found in muscle that bridges over 2 segments cranial and caudal from the operated segment. The craniocaudal distribution of endothelial cells is approximately the same. Somitocoele cells that are located centrally in the epithelial somite express the sclerotome-markers Pax-1 and Pax-9. After 2-3 days of reincubation, grafted thoracic somitocoele cells are found mainly in the cranial part of the caudal sclerotome half. They form an area representing the anlagen of the intervertebral disc and the rib. After longer reincubation periods, the grafted quail somitocoele cells form the intervertebral disc-homologous tissue and the proximal part of the rib. In more distal parts of the rib they are located in the cranial half of 1 rib and the caudal half of the next cranial rib. The somitocoele cells also form the surface of the intervertebral joint, and give rise to a small number of endothelial cells that are found up to 1 segment cranial and caudal to the operation site. Our studies show that resegmentation is found in most parts of the vertebra and in the distal ribs. One somite forms the origin and insertion of the segmental muscle. Therefore, the somite can be regarded as the ancestor of the vertebral motion segment. Somitocoele cells are located centrally both in the epithelial somite and in the vertebral motion segment.

Animals↗

Differences in the response of three embryologically distinct segments of the isolated canine posterior vena cava to vasoactive substances.

The canine posterior vena cava was excised and divided into three embryologically distinct segments: segment A (supradiaphragm), segment B-C (intrahepatic and that between liver and renal veins), and segment D (infrarenal). Circular and longitudinal strips were cut from each segment, suspended in Krebs bicarbonate solution and isometric tensions were recorded. The responses to six vasoactive agents, as well as transmural neural stimulation were studied. Maximum tension and ED50 were obtained for norepinephrine, epinephrine, acetylcholine, bradykinin, histamine and 5-hydroxytryptamine (5-HT). The responses were not only quantitatively, but qualitatively different among the three segments. Bradykinin constricted the strips in A and B-C but not in D. 5-HT (less than 10(-5) M) caused a dose-dependent contraction in A and D through its direct stimulating action, while in C, a contractile response appeared only after administration of a higher dose of 5-HT. This was due to an indirect sympathomimetic action of the agent. Segment B-C, which histologically contained massive longitudinal muscle bundles in the outer layer of the wall, exhibited spontaneous, rhythmic contractions. The existence of a cholinergic excitatory innervation, in addition to adrenergic, was demonstrated in C by transmural neural stimulation.

Acetylcholine↗

Active and passive mechanical properties of ring and spiral segments of isolated dog basilar artery assessed by electrical and pharmacological stimulations.

Contractile responses of dog basilar artery in forms of ring and spiral segments to electrical stimulation and vasoactive substances were studied. Ring segments always produced a larger contraction compared with spiral segments in response to various stimuli, while spiral segments produced contraction whose degree depended upon the angle of cut. The dose-response curves for electrical and pharmacological stimulations were almost identical for both ring and spiral segments when the contractile responses were expressed in relative terms, e.g. percent maximum and median effective dose (ED50). Functional and histological studies indicate that the difference in tension developed between ring and spiral segments is primarily attributable to the orientation of the smooth muscle cells. The results suggest that it depends on the purpose of the experiments and type of blood vessels whether ring or spiral segments should be chosen as the isolated vascular tissue.

Animals↗

Detection of calcified and noncalcified coronary atherosclerotic plaque by contrast-enhanced, submillimeter multidetector spiral computed tomography: a segment-based comparison with intravascular ultrasound.

BACKGROUND: We investigated the ability of multidetector spiral computed tomography (MDCT) to detect atherosclerotic plaque in nonstenotic coronary arteries. METHODS AND RESULTS: In 22 patients without significant coronary stenoses, contrast-enhanced MDCT (0.75-mm collimation, 420-ms rotation) and intravascular ultrasound (IVUS) of one coronary artery were performed. A total of 83 coronary segments were imaged by IVUS (left main, 19; left anterior descending, 51; left circumflex, 4; right coronary, 9). MDCT data sets were evaluated for the presence and volume of plaque in the coronary artery segments. Results were compared with IVUS in a blinded fashion. For the detection of segments with any plaque, MDCT had a sensitivity of 82% (41 of 50) and specificity of 88% (29 of 33). For calcified plaque, sensitivity was 94% (33 of 36) and specificity 94% (45 of 47). Coronary segments containing noncalcified plaque were detected with a sensitivity of 78% (35 of 45) and specificity of 87% (33 of 38), but presence of exclusively noncalcified plaque was detected with only 53% sensitivity (8 of 15). If analysis was limited to the 41 proximal segments (segments 1, 5, 6, and 11 according to American Heart Association classification), sensitivity and specificity were 92% and 88% for any plaque, 95% and 91% for calcified plaque, and 91% and 89% for noncalcified plaque. MDCT substantially underestimated plaque volume per segment as compared with IVUS (24+/-35 mm3 versus 43+/-60 mm3, P<0.001). CONCLUSIONS: The results indicate the potential of MDCT to detect coronary atherosclerotic plaque in patients without significant coronary stenoses. However, further improvements in image quality will be necessary to achieve reliable assessment, especially of noncalcified plaque throughout the coronary tree.

Calcinosis↗

Predictive value of 16-slice multidetector spiral computed tomography to detect significant obstructive coronary artery disease in patients at high risk for coronary artery disease: patient-versus segment-based analysis.

BACKGROUND: In this study, we investigated the diagnostic value and limitations of multidetector computed tomography (MDCT)-based noninvasive detection of significant obstructive coronary artery disease (CAD) in a consecutive high-risk patient population with inclusion of all coronary segments. METHODS AND RESULTS: In a prospective, blinded, standard cross-sectional technology assessment, a cohort of 33 consecutive patients with a positive stress test result underwent 16-slice MDCT and selective coronary angiography for the detection of significant obstructive CAD. We assessed the diagnostic accuracy of MDCT in a segment-based and a patient-based model and determined the impact of stenosis location and the presence of calcification on diagnostic accuracy in both models. Analysis of all 530 coronary segments demonstrated moderate sensitivity (63%) and excellent specificity (96%) with a moderate positive predictive value of 64% and an excellent negative predictive value (NPV) of 96% for the detection of significant coronary stenoses. Assessment restricted to either proximal coronary segments or segments with excellent image quality (83% of all segments) led to an increase in sensitivity (70% and 82%, respectively), and high specificities were maintained (94% and 93%, respectively). In a patient-based model, the NPV of MDCT for significant CAD was limited to 75%. Coronary calcification was the major cause of false-positive findings (94%). CONCLUSIONS: For all coronary segments included, 16-slice MDCT has moderate diagnostic value for the detection of significant obstructive coronary artery stenosis in a population with a high prevalence of CAD. The moderate NPV of patient-based detection of CAD suggests a limited impact on clinical decision-making in high-risk populations.

Coronary Angiography↗

The similarity of changes in segmental contraction patterns induced by postextrasystolic potentiation and nitroglycerin.

Despite a fundamental difference in their underlying mechanisms, both postextrasystolic potentiation (PESP) and administration of nitroglycerin (TNG) have been utilized to predict reversibility of abnormal segmental wall motion in patients with ischemic heart disease. To determine whether these interventions induce the same changes in segmental contraction pattern, we analyzed biplane ventriculograms of 14 patients who had an adequately visualized PESP beat on a basal ventriculogram as well as a post-TNG ventriculogram. Four segments in each plane were defined and the area ejection fraction of each segment was calculated for a basal sinus, PESP, and post-TNG beat. To correct for global differences in the response to PESP and TNG, we normalized each segmental ejection fraction (NSEF) by the ventricular ejection fraction for that beat and then compared the differences in NSEF from the basal value after PESP and TNG. Eleven patients demonstrated similar responses to both interventions. The three patients whose responses were discordant had elevated or unchanged left ventricular systolic or end-diastolic pressures at the time of the TNG ventriculogram. Our data suggest that, provided these pressures are lower than basal values at the time of the TNG ventriculogram, PESP and TNG will induce similar changes in segmental contraction patterns. Seven patients with similar responses had a PESP beat on their post-TNG ventriculogram. Changes in NSEF after PESP+TNG were identical to those after either intervention. This implies that the combination of interventions does not induce further changes in segmental contraction pattern beyond that produced by either intervention alone.

Angiocardiography↗

Effects of graded reductions in coronary perfusion pressure on the diastolic pressure-segment length relation and the rate of isovolumic relaxation in the resting conscious dog.

To assess the relations between coronary perfusion pressure, blood flow, and the diastolic pressure-segment length relation in the conscious animal, circumflex pressure was incrementally decreased in 10 resting, chronically instrumented dogs by a hydraulic occluding cuff while monitoring left ventricular pressure and regional segment length (with piezoelectric crystals) in the circumflex and left anterior descending territories. In five dogs, regional blood flow was measured by microsphere injections at selected circumflex pressures. The diastolic portion of the pressure-segment length curve was unchanged when decrements in circumflex pressure were within the autoregulatory range, that is, unassociated with changes in blood flow or systolic function. Further decrements in circumflex pressure, which decreased blood flow and regional segment shortening (both p less than 0.05), caused a progressive downward and rightward shift of the pressure-segment length curve (p less than 0.05). The rate of relaxation, as measured by tau (the time constant of pressure decay during isovolumic relaxation, which is calculated assuming either a fixed or a variable asymptote) and peak negative dP/dt, decreased slightly during reductions in circumflex pressure within the autoregulatory range and greatly at lower pressure (all p less than 0.05). Thus, in the conscious animal, reductions in coronary perfusion pressure within the autoregulatory range do not affect the diastolic pressure-segment length curve but cause modest decreases in the rate of isovolumic relaxation. Further reductions in coronary perfusion pressure, below the limits of blood flow autoregulation, cause an increased extent of relaxation with a marked downward shift of the diastolic pressure-segment length curve as well as a large decrease in the rate of relaxation.

Animals↗

Chronotropic response to exercise. Improved performance of ST-segment depression criteria after adjustment for heart rate reserve.

BACKGROUND: Heart rate (HR) response to exercise plays an important role in the diagnosis of coronary artery disease (CAD). Adjustment of ST-segment depression for the change in HR with exercise increases the accuracy of the exercise ECG in the detection of CAD. In addition, an attenuated HR response to exercise, a manifestation of chronotropic incompetence, may have independent diagnostic value for CAD. METHODS AND RESULTS: The diagnostic value of adjusting the magnitude of ST-segment depression, the ST-segment (ST)/HR index, and the ST/HR slope for chronotropic response to exercise was assessed in 283 control subjects and 337 patients with CAD by dividing each ST measurement by the fraction of HR reserve achieved. At a matched specificity of 96%, ST-segment depression of > 160 microV identified CAD with a sensitivity of 52%, an ST/HR index of > 1.69 microV/bpm identified CAD with a sensitivity of 90%, and an ST/HR slope of > 2.96 microV/bpm identified CAD with a sensitivity of 88%. Adjustment for HR reserve improved the sensitivity of each method: adjusted ST-segment depression of > 176 had a sensitivity of 87% (P < .0001), an adjusted ST/HR index of > 2.14 had a sensitivity of 94% (P = .005), and an adjusted ST/HR slope of > 3.47 had a sensitivity of 93% (P = .0001). In addition, the 94% and 93% sensitivities of the adjusted ST/HR index and ST/HR slope were significantly greater than the 87% sensitivity of adjusted ST-segment depression (P < .0001). CONCLUSIONS: Correction for an attenuated HR response to exercise improves performance of the simple and HR-adjusted ST-segment depression criteria for the identification of CAD. These findings support assessment of the degree of chronotropic reserve in routine evaluation of the exercise ECG.

Coronary Disease↗

Mechanisms of augmented segment shortening in nonischemic areas during acute ischemia of the canine left ventricle.

To examine the interaction between normal and nonischemic areas of the left ventricle during acute ischemia, we implanted midwall ultrasonic segment length gauges in the ischemic zone and in nonischemic areas of the canine left ventricle. During acute ischemia, end-diastolic pressure and segment length in the nonischemic areas increased. There was no change from control in the segment length at the time of aortic valve opening and closure. Thus, in nonischemic areas, total segment shortening, as measured by the percent change in segment length from the time of end-diastole to aortic valve closure, increased. This was due to an increase in isovolumic shortening (end-diastole to aortic valve opening) with no change in ejection shortening (aortic valve opening to closure). The progressive increase in isovolumic shortening in nonischemic areas over time was directly paralleled by the progressive development of the isovolumic lengthening or bulge in the ischemic zone. Nonischemic areas, whether adjacent, on the opposite wall, or distant to the ischemic zone, all behaved similarly. Adrenergic blockade did not qualitatively alter these findings. We conclude that acute ischemia induces a mechanical disadvantage which is greater than just the loss of contractile function by the ischemic segment. Despite the apparent hyperfunction of nonischemic areas, the increased total segment shortening is expended in stretching the ischemic zone during isovolumic systole. As a result, there is no significant "compensatory" increase in ejection shortening in nonischemic areas.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗