Confirmation of brevetoxin metabolism in cockle, Austrovenus stutchburyi, and greenshell mussel, Perna canaliculus, associated with New Zealand neurotoxic shellfish poisoning, by controlled exposure to Karenia brevis culture.

We examined metabolism of PbTxs in New Zealand cockle, Austrovenus (A.) stutchburyi, and greenshell mussel, Perna (P.) canaliculus, by means of liquid chromatography coupled with tandem mass spectrometry. PbTx-2, PbTx-3 and BTX-B5 were detected in Karenia (K.) brevis culture medium in the ratio of ca. 50:2:5. The amounts of PbTx-3 and BTX-B5 were greatly increased in both seawater and shellfish exposed to K. brevis cultures or supernatant prepared by disruption of K. brevis under appropriate condition, while those of PbTx-2 were decreased. Some PbTx-2 was present in P. canaliculus, but not in A. stutchburyi. Low levels of BTX-B1 were detected in A. stutchburyi, but not P. canaliculus. Levels of PbTx-3 and BTX-B5 were highest immediately after exposure and then declined rapidly in both shellfish. BTX-B1 increased in concentration after exposure, and was then gradually eliminated from A. stutchburyi. Three successive exposures of A. stutchburyi to K. brevis cultures resulted in similar initial levels of PbTx-3 and BTX-B5, while BTX-B1 accumulated after each dose. In P. canaliculus, initial levels of PbTx-3 were similar, while PbTx-2 and BTX-B5 accumulated after each dose. PbTx-3 and BTX-B5 are proposed to be suitable markers for monitoring shellfish toxicity after a red tide event.     

Estimation of paracrine signaling using quantitative RT-PCR from multiple patchy lesion samples

We investigated whether correlations between mRNA levels of cytokines versus other proteins from patchy lesion could estimate cytokine paracrine signaling in vivo. Experiments with rat experimental autoimmune myocarditis (EAM), a patchy myocarditis model, indicated IL-1 and other protein levels were correlated, indicating paracrine signaling pathways in vivo.     

Health-related quality of life of outpatients with systolic and isolated diastolic dysfunction

Background The impact of isolated diastolic dysfunction (IDD) and systolic dysfunction (SD) on health-related quality of life (HRQOL) is unknown. Methods and Results To evaluate HRQOL in patients with IDD and SD under treatment, information on outpatients aged 60-84 years was extracted from the records of 4,500 consecutive individuals who underwent echocardiographic examination at Sado General Hospital. The medical records of these patients were reviewed and a questionnaire, including the Medical Outcome Study Short Form 36, was mailed to 71 IDD and 99 SD patients; answers were obtained from 66 and 91 patients, respectively. The HRQOL of patients with cardiac dysfunction was impaired even when echocardiographic parameters improved with treatment. Patients with IDD showed an impairment of HRQOL similar to those with SD. Compared with males, female patients had a larger and more significant reduction in the physical and mental components of the HRQOL score. These scores correlated positively with exercise capacity in patients with IDD or SD. Conclusions Impaired HRQOL, in both its mental and physical components, is a serious problem for IDD and SD patients under treatment. Because exercise intolerance may underlie the reduced HRQOL, improving exercise capacity could be an important target for managing outpatients with heart failure. (Circ J 2008; 72: 1436 - 1442).     

Coronary blood flow in evolving myocardial infarction preceded by preinfarction angina: a critical reevaluation of preconditioning effects in clinical cases

This study was undertaken to reevaluate the protective effects of preinfarction (pre-MI) angina in acute MI. The mechanisms involved in the apparent protective effects of pre-MI angina have been presumed to be preconditioning effects as defined by experimental studies. The phenomenon, has not, however, been observed in diabetic and/or elderly patients or in those treated by primary percutaneous coronary intervention (PCI). A total of 202 patients with anterior wall MI without a history of MI who underwent primary PCI with coronary balloon dilation and stenting (rate: 50%) <6 hours after onset were studied. Patients included 59 with pre-MI angina (group 1) and 143 without pre-MI angina (group 2). The infarct-related coronary artery was patent on admission in 46% of group 1 and 31% of group 2 (p=0.045). Thrombolysis in Myocardial Infarction (TIMI) 1-2 flow was significantly more frequent in group 1 (29%) than in group 2 (11%, p=0.005) on admission. Among risk factors, clinical background, coronary anatomy, and clinical outcome, the only significant predictor of pre-MI angina was a patent infarct-related coronary artery on admission (odds ratio: 2.39, p = 0.015). There was no significant difference in left ventricular ejection fraction, peak creatine kinase, or the incidences of heart failure and in-hospital/follow-up deaths between these groups. In conclusion, the findings suggest that the protective effects reported in MI with pre-MI angina treated by thrombolysis are due to more fragile thrombotic occlusion, which can be more easily recanalized by thrombolysis, whereas the beneficial effects are not evident in those treated by primary PCI.     

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.