One of the primary consequences of left ventricular dysfunction (LVD) after myocardial infarction is a decrement in exercise capacity. Several factors have been hypothesized to account for this decrement, including alterations in skeletal muscle metabolism and aerobic capacity. The purpose of this study was to determine whether LVD-induced alterations in skeletal muscle enzyme activities, fiber composition, and fiber size are 1) generalized in muscles or specific to muscles composed primarily of a given fiber type and 2) related to the severity of the LVD. Female Wistar rats were divided into three groups: sham-operated controls (n = 13) and rats with moderate (n = 10) and severe (n = 7) LVD. LVD was surgically induced by ligating the left main coronary artery and resulted in elevations (P < 0.05) in left ventricular end-diastolic pressure (sham, 5 +/- 1 mmHg; moderate LVD, 11 +/- 1 mmHg; severe LVD, 25 +/- 1 mmHg). Moderate LVD decreased the activities of phosphofructokinase (PFK) and citrate synthase in one muscle composed of type IIB fibers but did not modify fiber composition or size of any muscle studied. However, severe LVD diminished the activity of enzymes involved in terminal and beta-oxidation in muscles composed primarily of type I fibers, type IIA fibers, and type IIB fibers. In addition, severe LVD induced a reduction in the activity of PFK in type IIB muscle, a 10% reduction in the percentage of type IID/X fibers, and a corresponding increase in the portion of type IIB fibers. Atrophy of type I fibers, type IIA fibers, and/or type IIB fibers occurred in soleus and plantaris muscles of rats with severe LVD. These data indicate that rats with severe LVD after myocardial infarction exhibit 1) decrements in mitochondrial enzyme activities independent of muscle fiber composition, 2) a reduction in PFK activity in type IIB muscle, 3) transformation of type IID/X to type IIB fibers, and 4) atrophy of type I, IIA, and IIB fibers.

These findings are consistent with the hypothesis that the adaptive response to treadmill running may require elevations in the expression of HSP60 and GRP75 to support protein import and folding.

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Kansas (DCP)S U M M A R Y The hamster is a valuable biological model for physiological investigation. Despite the obvious importance of the integration of cardiorespiratory and muscular system function, little information is available regarding hamster muscle fiber type and oxidative capacity, both of which are key determinants of muscle function. The purpose of this investigation was to measure immunohistochemically the relative composition and size of muscle fibers composed of types I, IIA, IIX, and IIB fibers in hamster skeletal muscle. The oxidative capacity of each muscle was also assessed by measuring citrate synthase activity. Twenty-eight hindlimb, respiratory, and facial muscles or muscle parts from adult (144-147 g bw) male Syrian golden hamsters ( n ϭ 3) were dissected bilaterally, weighed, and frozen for immunohistochemical and biochemical analysis. Combining data from all 28 muscles analyzed, type I fibers made up 5% of the muscle mass, type IIA fibers 16%, type IIX fibers 39%, and type IIB fibers 40%. Mean fiber cross-sectional area across muscles was 1665 Ϯ 328 m 2 for type I fibers, 1900 Ϯ 417 m 2 for type IIA fibers, 3230 Ϯ 784 m 2 for type IIX fibers, and 4171 Ϯ 864 m 2 for type IIB fibers. Citrate synthase activity was most closely related to the population of type IIA fibers ( r ϭ 0.68, p Ͻ 0.0001) and was in the rank order of type IIA Ͼ I Ͼ IIX Ͼ IIB. These data demonstrate that hamster skeletal muscle is predominantly composed of type IIB and IIX fibers.

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Abnormalities intrinsic to skeletal muscle are thought to contribute to decrements in exercise capacity found in individuals with chronic heart failure (CHF). Na+-K+-adenosinetriphosphatase (the Na+ pump) is essential for maintaining muscle excitability and contractility. Therefore, we investigated the possibility that the number and affinity of Na+ pumps in locomotor muscles of rats with CHF are decreased. Myocardial infarction (MI) was induced in 8 rats, and a sham operation was performed in 12 rats. The degree of CHF was assessed approximately 180 days after surgery. Soleus and plantaris muscles were harvested, and Na+ pumps were quantified by using a [3H]ouabain binding assay. At the time of muscle harvest, MI and sham-operated rats were similar in age (458 +/- 54 vs. 447 +/- 34 days old, respectively). Compared with their sham-operated counterparts, MI rats had a significant amount of heart failure, right ventricular-to-body weight ratio was greater (48%), and the presence of pulmonary congestion was suggested by an elevated lung-to-body weight ratio (29%). Left ventricular end-diastolic pressure was significantly increased in the MI rats (11 +/- 1 mmHg) compared with the sham-operated controls (1 +/- 1 mmHg). In addition, mean arterial blood pressure was lower in the MI rats compared with their control counterparts. [3H]ouabain binding sites were reduced 18% in soleus muscle (136 +/- 12 vs. 175 +/- 13 pmol/g wet wt, MI vs. sham, respectively) and 22% in plantaris muscle (119 +/- 12 vs. 147 +/- 8 pmol/g wet wt, MI vs. sham, respectively). The affinity of these [3H]ouabain binding sites was similar for the two groups. The relationship between the reduction in Na+ pump number and the reduced exercise capacity in individuals with CHF remains to be determined.

In patients with portopulmonary hypertension (n = 13) included in the 12-week randomized placebo-controlled PATENT-1 trial, riociguat was well tolerated and improved 6-min walking distance (6MWD), World Health Organization functional class (WHO FC), and other efficacy parameters; 6MWD and WHO FC improvements were sustained over two years in the open-label extension, PATENT-2.

We present a new mass-transfer model for simulating industrial nylon-6 polymerization trains. In this model, both diffusion and boiling (bubble nucleation) contribute to mass transfer. With this model, we are able to simulate widely differing production technologies using identical mass-transfer parameters, along with identical models for fundamentals such as phase equilibrium, physical properties, and polymerization kinetics. To illustrate, we simulate the direct-melt process and the bubble-gas kettle process. The direct-melt process builds up the polymer molecular weight and removes nearly all residual caprolactam monomer by employing, under vacuum, a wiped-wall evaporator and a rotating-disk finisher. The bubble-gas kettle process, on the other hand, injects inert gas bubbles through the melt at nearly atmospheric pressure to build up the polymer molecular weight but does not significantly reduce the caprolactam level because the diffusion coefficient is so low. We validate our process models using commercial train performance data at different production rates, including the first known validation of a dynamic rate-change simulation for industrial polycondensation trains. Model predictions quantitatively agree with product quality data such as formic acid viscosity (FAV), polymer end-group concentration, and water extractables. The prediction errors for the direct-melt process are 2.81%, −3.13%, and −3.06% for FAV, water extractables, and amine end groups, respectively. For the bubble-gas kettle process, the prediction errors are −17.2%, −17.0%, and −7.49% for extrusion FAV, washed-and-dried FAV, and water extractables, respectively. These errors are much lower than the ca. −50% errors obtained by existing advanced models for devolatilization.