Hibernating myocardium due to chronic repetitive ischemia is associated with regional sympathetic nerve dysfunction and spontaneous arrhythmic death in the absence of infarction. Although inhomogeneity in regional sympathetic innervation is an acknowledged substrate for sudden death, the mechanism(s) responsible for these abnormalities in viable, dysfunctional myocardium (i.e., neural stunning vs. sympathetic denervation) and their association with nerve sprouting are unknown. Accordingly, markers of sympathetic nerve function and nerve sprouting were assessed in subendocardial tissue collected from chronically instrumented pigs with hibernating myocardium (n = 18) as well as sham-instrumented controls (n = 7). Hibernating myocardium exhibited evidence of partial sympathetic denervation compared with the normally perfused region and sham controls, with corresponding regional reductions in tyrosine hydroxylase protein (-32%, P < 0.001), norepinephrine uptake transport protein (-25%, P = 0.01), and tissue norepinephrine content (-45%, P < 0.001). Partial denervation induced nerve sprouting with regional increases in nerve growth factor precursor protein (31%, P = 0.01) and growth associated protein-43 (38%, P < 0.05). All of the changes in sympathetic nerve markers were similar in animals that developed sudden death (n = 9) compared with electively terminated pigs with hibernating myocardium (n = 9). In conclusion, sympathetic nerve dysfunction in hibernating myocardium is most consistent with partial sympathetic denervation and is associated with regional nerve sprouting. The extent of sympathetic remodeling is similar in animals that develop sudden death compared with survivors; this suggests that sympathetic remodeling in hibernating myocardium is not an independent trigger for sudden death. Nevertheless, sympathetic remodeling likely contributes to electrical instability in combination with other factors.

Regional reductions in norepinephrine-tracer uptake are found in pigs with hibernating myocardium. Clinical studies would suggest that this is evidence for denervation; however, the functional responses to sympathetic stimulation have not been evaluated, and our previous studies with beta-adrenergic stimulation have not suggested denervation hypersensitivity. Therefore, pigs were chronically instrumented to produce hibernating myocardium characterized by chronic regional dysfunction and histological viability. Open-chest studies were performed to determine changes in regional function in response to both pre- and postjunctional stimulation. Regional segment shortening was reduced at rest in hibernating myocardium compared with controls (13 +/- 3% vs. 27 +/- 3%, P = 0.004). During stellate ganglion stimulation, regional function increased in both groups of animals (P = 0.008 vs. baseline), but the increase in hibernating myocardium was blunted compared with controls (Delta%, 3 +/- 2% vs. 8 +/- 3%, P = 0.04). Similar results occurred with intracoronary tyramine (10 mug/kg). Functional improvement during intravenous epinephrine infusion (0.35 mug.kg(-1).min(-1)) was also blunted in hibernating myocardium compared with controls (Delta%, 7 +/- 1% vs. 15 +/- 2%, P = 0.04). Even when the improvement in function was expressed relative to the reduced baseline, there was no evidence for catecholamine-mediated hypersensitivity in hibernating myocardium. We therefore conclude that functional responses to both pre- and postjunctional sympathetic stimulation are blunted in pigs with hibernating myocardium. In contrast to previous studies of infarcted, denervated, and acutely stunned myocardium, there is no catecholamine-induced hypersensitivity in hibernating myocardium. These data suggest a downregulation in functional responses to stimulation that would protect hibernating myocardium from demand-induced ischemia at the expense of contractile reserve during sympathetic stimulation.

Altered ventricular repolarization manifested as QT-RR hysteresis occurs in Long QT Syndrome and with acute ischemia. We hypothesized that this might identify risk of sudden cardiac death (SCD) associated with chronic coronary disease. Pigs were chronically instrumented with a left anterior descending (LAD) coronary stenosis to produce hibernating myocardium (n=11). This model develops frequent, spontaneous SCD due to ventricular tachycardia degenerating into ventricular fibrillation, in the absence of infarction. As compared to 13 Controls there was reduced LAD wall-thickening (25±2 vs 54±9%, p<0.001) and flow reserve (1.4±0.3 vs 2.7±0.5, p<0.05), with preserved ejection fraction (63±3 vs 71±4%, p=0.09), and minimal necrosis (0.4±0.2% of LV). Regional electrograms were obtained from subendocardial piezoelectric crystals. Baseline QT intervals from the LAD region were similar in both groups (Hibernating – 354±13 vs. 356±15 ms in Controls, p=0.93). The QT intervals shortened to a similar extent during atrial pacing (Hibernating – 247±8 vs. 249±10 ms, p=0.92), stellate ganglion stimulation (Hibernating – 259±16 vs. 242±11 ms, p=0.37), and intravenous epinephrine infusion (Hibernating – 255±16 vs. 237±9 ms, p=0.31), with no differences between groups. In contrast, the LAD region QT-RR relationships during epinephrine stimulation were altered in pigs with hibernating myocardium, resulting in greater hysteresis loop areas as compared to Controls (7247±2334 vs 1927±943 ms 2 , p<0.05). Interestingly, this did not reflect stress-induced ischemia since pigs with hibernating myocardium also had greater hysteresis loop areas in the remote normally-perfused regions (9295±1319 ms 2 , p=0.40 vs LAD). There were no significant regional differences in either group. Hibernating myocardium in pigs is associated with altered ventricular repolarization hysteresis. This abnormality is global, and thus dissociated from regional dysfunction, reduced flow reserve and the propensity to develop acute ischemia. Thus, dynamic alterations in ventricular repolarization may be a substrate for SCD in patients with ischemic heart disease and chronic remodeling from hibernating myocardium.

Для обнаружения малоразмерных малозаметных низколетящих низкоскоростных целей на малой дальности требуется синтезатор стабильных частот и сигналов с минимальным уровнем фазового шума, большим динамическим диапазоном по побочным спектральным составляющим и высокой скоростью перестройки частоты. В данной работе формулируется оптимизационная задача структурно-параметрического синтеза, рассматриваются методы ее решения и определяются базовые алгоритмы для получения общего решения задачи синтеза. Ключевые слова: прямой цифровой синтез; косвенный синтез; синтезатор стабильных частот; спектральная плотность мощности фазового шума; структурно-параметрическая оптимизация; динамический диапазон по побочным спектральным составляющим; время перестройки частоты; радиолокационная станция. To detect small-scale low-visible low-fl ying low-speed targets at short range, one needs a synthesizer of stable frequencies and signals with a minimum level of phase noise, a large dynamic range along the side spectral components and a high speed of frequency tuning. The paper formulates the optimization problem of structural-parametric synthesis, considers the methods for solving it, and determines the basic algorithms for obtaining a general solution of the synthesis problem.