Rate-dependent changes in atrial action potential duration after short- duration rapid atrial pacing in humans.

The effect of rapid atrial pacing on the rate adaptation of the atrial action potential duration was studied in humans. The right atrial monophasic action potential (RAMAP) of 5 patients was recorded before and after 30 min of rapid atrial pacing. The pacing cycle length (CL) was 146 +/- 9 ms, the shortest duration at which 1:1 capture was possible. The RAMAP duration at 90% repolarization (RMAPD) was measured. CL-dependent changes in RAMAPD (CL 600 ms-CL 300 ms) before and after rapid atrial pacing were 51.8 +/- 10.7 ms and 30.8 +/- 7.6 ms (p < 0.05), respectively.     

Unusual radiological findings of Fasciola hepatica infection with huge cystic and multilocular lesions

This report describes a case of hepatic phase Fasciola hepatica infection presenting huge and multilocular lesions. The unique radiological findings mimicked hydatid diseases and also cystic liver neoplasm. Fascioliasis should be included in the differential diagnosis for cystic liver diseases.     

Cytokine-induced nitric oxide inhibits mitochondrial energy production and induces myocardial dysfunction in endotoxin-treated rat hearts

The mechanism responsible for cardiac depression in septic shock remains unknown. The present study examined whether nitric oxide (NO) overproduced by inducible NO synthase (iNOS) can inhibit aerobic energy metabolism and impair the myocardial function in endotoxin-treated rat hearts. Lipopolysaccharide (LPS) significantly decreased systolic blood pressure (BP) to 44% of control during the 48 h treatment. Hearts from control and LPS-treated rats were perfused in a Langendorff apparatus. After LPS injection, left ventricular (LV) developed pressure (LVDP) was significantly depressed, plasma NO2-/NO3- (NO(x)) concentration was markedly increased, and myocardial adenosine 5'-triphosphate (ATP), creatine phosphate (CrP), and the ratio of ATP/adenosine 5'-diphosphate were progressively decreased with time. Immunological examination showed a significant expression of iNOS protein in the LPS-treated myocytes. Aminoguanidine, an inhibitor of iNOS, significantly attenuated these LPS-induced functional and metabolic changes. Myocardial cyclic guanosine 3',5'-monophosphate (cGMP) content was significantly increased after LPS injection. Methylene blue, an inhibitor of soluble guanylate cyclase, blunted this increase in cGMP and significantly restored the LPS-induced contractile dysfunction 6 h after LPS injection. In addition, there was a significant negative correlation between LVDP and myocardial cGMP levels as well as a significant negative correlation between LVDP and plasma NO(x) levels. In contrast, 48 h after LPS injection, methylene blue no longer affected cardiac performance, and there was a significant positive correlation between LVDP and myocardial ATP content. Furthermore, the normalized activities (as a ratio of the citrate synthase activity) of mitochondrial NADH-CoQ reductase, succinate-CoQ reductase, and ATPase, were significantly inhibited, and the swelling or disruption of mitochondria cristae was seen in the 48 h LPS treatment. These LPS-induced functional and morphological disorders in the mitochondria were significantly improved by aminoguanidine. The findings suggest that sustained production of NO by iNOS leads to contractile dysfunction via cGMP in the early stage, but that it can directly impair the mitochondrial function, lower myocardial energy production, and contribute significantly to the myocardial dysfunction in the later stage of septic shock.     

Improvement of endothelial dysfunction by angiotensin II blockade accompanied by induction of vascular hepatocyte growth factor system in diabetic spontaneously hypertensive rats

 Hepatocyte growth factor (HGF) is a unique growth factor with many protective functions. Previously, we demonstrated that HGF stimulated growth of endothelial cells without replication of vascular smooth muscle cells (VSMC) and that angiotensin (Ang) II significantly decreased local HGF production in VSMC. Moreover, we also reported that high glucose significantly decreased local vascular HGF production. Therefore, we examined effects of Ang II blockade on vascular HGF expression and endothelial injury in diabetic hypertensive rats. An angiotensin-converting enzyme inhibitor (quinapril) and an Ang II type 1 receptor antagonist (GA-0113) or vehicle was administrated to diabetic spontaneously hypertensive rats (SHR-DM), in whom diabetes was induced by streptozotocin. Endothelial function was evaluated by the vasodilator response to acetylcholine, and the expression of vascular HGF and its receptor, c-met, was examined by immunohistochemistry. Both quinapril and GA-0113 significantly improved the vasodilator response to acetylcholine (P < 0.01), while vehicle did not as compared to untreated normotensive Wistar-Kyoto rats (WKY). We next examined the effects of Ang II blockade on vascular HGF expression in SHR-DM. Importantly, the vascular HGF level was markedly decreased in SHR-DM as compared to WKY, while Ang II blockade by quinapril or GA-0113 significantly increased positive staining for HGF in SHR-DM. Similarly, staining of its specific receptor, c-met, was less in the blood vessels of SHR-DM as compared to WKY. In contrast, Ang II blockade also significantly increased c-met production in SHR-DM. The present data demonstrated the improvement of endothelial dysfunction by Ang II blockade in SHR-SM, accompanied by an increase in vascular HGF and c-met. Received: June 7, 2002 / Accepted: September 21, 2002 Acknowledgments We wish to thank Rie Kosai and Keiko Yamaguchi for their excellent technical assistance. This work was partially supported by grants from the Japan Health Sciences Foundation, a Grant-in-Aid from The Ministry of Public Health and Welfare, a Grant-in-Aid for the Development of Innovative Technology, a Grant-in-Aid from Japan Promotion of Science, and through Special Coordination Funds of the Ministry of Education, Culture, Sports, Science and Technology, the Japanese Government. Correspondence to N. Tomita     

Long-term follow-up of atrioventricular delay optimization in patients with biventricular pacing.

BACKGROUND: Atrioventricular (AV) delay optimization may be important in patients with biventricular pacing and the optimal AV delay can be predicted using Doppler echocardiography and the formula: optimal AV delay = AV delay-the interval between the end of A wave and complete closure of the mitral valve when the AV delay is set at slightly prolonged AV delay. METHODS AND RESULTS: In the present study the efficacy of this method was evaluated in 5 patients (67.4+/-8.0 (SD) years old) with biventricular pacing. Cardiac output (CO) and diastolic filling time were measured by Doppler echocardiography. When the AV delay was set at the predicted optimal AV delay -25 ms, the predicted optimal AV delay (133+/-66 ms) and predicted optimal AV delay + 25 ms, the respective CO were 4.5+/-0.9, 5.3+/-1.0, 4.8+/-1.0 L/min (p<0.05, ANOVA) and the diastolic filling times were 364 +/-100, 373+/-105, 335+/-84 ms (p<0.05, ANOVA). Congestive heart failure improved from New York Heart Association class 3.6+/-0.5 to 1.4+/-0.5 (p<0.001). CONCLUSIONS: AV delay optimization is important in patients with biventricular pacing and can be easily achieved by the new method.     

Autonomic responses to orthostatic stress in head-up tilt testing: Relationship to test-induced prolonged asystole

Background: Prolonged asystole is sometimes an extreme manifestation of neurally mediated syncope. Hypothesis: To investigate the mechanism of head-up tilt testing-induced prolonged (life-threatening) cardiac asystole, we measured temporal changes in frequency domain heart rate variability indices in 25 patients with syncope of undetermined etiology. Methods: Head-up tilt testing (80°) was performed in 25 patients for up to 40 min or until asystole or syncope occurred. Three patients (Group 1; 37 ±13 years, 1 man, 2 women) had an episode of prolonged cardiac asystole (≥ 10 s) during testing, necessitating cardiopulmonary resuscitation. Syncope, but no asystole, was induced in 10 patients (Group 2; 48 ± 31 years, 6 men, 4 women), and 12 patients (Group 3; 55 ± 20 years, 5 men, 7 women) failed to show asystole or syncope during testing. Power spectra of low (0.04–0.15 Hz) and high (0.15–0.40 Hz) frequency, and total (0.01–1.00 Hz) frequency spectra were measured in consecutive 2 min segments throughout the test. Results: Maximally changed values in heart rate, systolic blood pressure, and heart rate variability indices during testing were compared among the three groups (maximally changed values did not include the values during tilt-induced symptoms). High frequency spectra in Groups 2 and 3, but not in Group 1, decreased during the test. High frequency spectra, low frequency spectra, and total spectra in Group 1 were significantly higher than those in Groups 2 and 3 during testing. In Group 1 patients, findings at test-induced asystole were consistent with exaggerated sympathetic and concurrent persistent parasympathetic activity. Conclusion: Unusual autonomic responses to orthostatic stress can cause prolonged asystole, and this autonomic nerve dysregulation may relate to asystolic episodes associated with cardiovascular collapse.     

Insulin resistance in nondiabetic patients is associated with expansive remodeling in coronary arterial lesions

OBJECTIVE: Insulin resistance has been implicated as an important initiating factor in coronary atherosclerosis. However, associations between insulin resistance and specific morphologic features of atherosclerotic coronary arteries remain unclear. We ultrasonographically evaluated the morphologic features of atherosclerotic coronary arteries in nondiabetic patients with insulin resistance. METHODS: Before intervention, 90 patients with 105 culprit lesions underwent intravascular ultrasound examination through which vessel area, lumen area and plaque area were evaluated. Expansive remodeling (lesion vessel area more than 5% greater than at the proximal reference segment) and constrictive remodeling (lesion vessel area more than 5% less than at the distal reference segment) were also evaluated. Insulin resistance was determined by homeostasis model assessment and defined as values above the 75th percentile (that is, 1.71). RESULTS: Insulin-resistant patients numbered 23, while nonresistant patients numbered 67. Culprit lesions in the insulin-resistant group showed larger vessel area (18.16 +/- 6.94 compared with 13.64 +/- 4.28 mm, P = 0.0001) and plaque area (16.64 +/- 6.78 compared with 12.05 +/- 4.12 mm, P = 0.0001) and more frequently showed expansive remodeling (56% compared with 14%, P < 0.0001) and calcific plaque (33% compared with 12%, P = 0.01). Multivariable logistic regression analysis identified only insulin resistance (odds ratio, 4.9, P = 0.008) as an independent predictor of expansive remodeling. CONCLUSIONS: Insulin resistance independently predicted expansive remodeling, underscoring the importance of insulin resistance in coronary atheroscrelosis.     

Ventricular septal rupture masquerading as coronary perforation during intervention for acute myocardial infarction

Ventricular septal rupture is a serious complication of acute myocardial infarction. We experienced a case of septal rupture immediately after primary angioplasty with thrombolysis, whose angiographic findings were similar to those of coronary perforation. The progression of septal rupture was delineated by the serial angiograms. Catheter Cardiovasc Interv 2004;62:466–470. © 2004 Wiley‐Liss, Inc.